Research Fellow
+39.089.964026
Academic Curriculum
Diego Caccavo graduated with honors in Chemical Engineering in 2013 at the University of Salerno with a thesis entitled “Mathematical description of hydrogels’ behavior for biomedical applications”, carried out in part at Chalmers University of Technology (Sweden ).
In 2017 he obtained the title of PhD in Industrial Engineering, Chemical Engineering curriculum, at the Industrial Engineering Departments (DIIN) of the University of Salerno, with a thesis entitled “Analysis and modeling of the behavior of hydrogels- based systems for biomedical and agro-food applications “.
Since 2017, as a research fellow, he has been working at the University of Salerno in the departments of Pharmacy and Industrial Engineering. Since 2022 he has been a researcher at the Department of Industrial Engineering.
The didactic activity of Eng. Diego consisted of monographic seminars and collaborations in the courses of Principles of Chemical Engineering (2014/2017), Transport Phenomena in Food Processes (2014/2021) and Food Chemical Reactors (2014/2021) at DIIN, courses for which he participated as an expert on the subject in the examination committees.
He teaches in the courses of “Process Instrumentation and Control / Instrumentation and Control of Chemical Processes”, of “Food Chemical Reactors” and “Mathematical Modeling and Control for the Process Industry”.
He has also tutored for the development of more than 40 degree theses in Chemical Engineering, of which more than a third are master’s degrees.
His research activities concern:
- the analysis and modeling of the behavior of hydrogel-based systems for biomedical and agri-food applications.
- the development of innovative methods, such as the coaxial jet mixer, for the production of nanoparticles, with particular emphasis on the production and characterization of liposomes.
- the development and control of new processes (and products), based on the application of the concepts of transport phenomena and rapid prototyping (electronics and materials).
He is a founding partner of two Spin-Offs, Eng4Life S.r.L. (https://www.eng4life.it) and EST S.r.L. (http://est.srl).He is the inventor in two Italian patent applications, the first concerning a method of measuring the alcohol content in beverages by analyzing the vapor phase above them and the second relating to a method and instrument for controlling the pH in simulating solutions. gastric environment.
Eng. Diego Caccavo is reviewer for numerous international magazines of the ISI circuit. He is part of the editorial board of the prestigious international journal European Journal of Pharmaceutics and Biopharmaceutics (Elsevier, IF 2021 5.589). He has produced more than 30 publications in international journals, indexed on the Web Of Science and Scopus databases. In May 2021, according to Scopus, the h-index was 12 (33 registered works, 417 citations). He is among the “Top Scientists 2019-2020”, a database that collects about 2% of the best researchers in the world, recently published in the international scientific journal PlosBiology (10.1371 / journal.pbio.3000918).
Publications
2024 |
Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela Analysis and simulation of wet-granulation processes Journal Article Journal of the Taiwan Institute of Chemical Engineers, 159 (105455), 2024. Abstract | Links | BibTeX | Tags: Dynamic image analysis, Modeling, Particle size distribution, Population balance equation, Wet-granulation @article{Caccavo2024, title = {Analysis and simulation of wet-granulation processes}, author = {Diego Caccavo and Gaetano Lamberti and Anna Angela Barba}, url = {https://doi.org/10.1016/j.jtice.2024.105455}, year = {2024}, date = {2024-03-22}, journal = {Journal of the Taiwan Institute of Chemical Engineers}, volume = {159}, number = {105455}, abstract = {Size enlargement by wet-granulation is one of the most important unit operation in several industrial fields: pharmaceutics, food processing, animal nutrition, agronomics, and so on. A lot of techniques have been used in order to measure the particle size distributions (PSD) and a few different approaches are available to model the PSD evolution during the process, mainly based on population balance equations (PBE). However, difficulties in both the activities (reliable measurement and robust modeling) have hindered their diffusion in industrial practice, keeping the granulation closer to an art than to a science.}, keywords = {Dynamic image analysis, Modeling, Particle size distribution, Population balance equation, Wet-granulation}, pubstate = {published}, tppubtype = {article} } Size enlargement by wet-granulation is one of the most important unit operation in several industrial fields: pharmaceutics, food processing, animal nutrition, agronomics, and so on. A lot of techniques have been used in order to measure the particle size distributions (PSD) and a few different approaches are available to model the PSD evolution during the process, mainly based on population balance equations (PBE). However, difficulties in both the activities (reliable measurement and robust modeling) have hindered their diffusion in industrial practice, keeping the granulation closer to an art than to a science. |
2023 |
Mancino, Raffaele; Caccavo, Diego; Barba, Anna Angela; Lamberti, Gaetano; Biasin, Alice; Cortesi, Angelo; Grassi, Gabriele; Grassi, Mario; Abrami, Michela Agarose Cryogels: Production Process Modeling and Structural Characterization Journal Article Gels, 9 (9), pp. 765, 2023, ISSN: 23102861. Abstract | Links | BibTeX | Tags: Agarose, cryogels, Equilibrium, Hydrogels, Modeling, Rheology @article{Mancino2023, title = {Agarose Cryogels: Production Process Modeling and Structural Characterization }, author = {Raffaele Mancino and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti and Alice Biasin and Angelo Cortesi and Gabriele Grassi and Mario Grassi and Michela Abrami}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85172281028&doi=10.3390%2fgels9090765&partnerID=40&md5=7753d30977c1b97694c4ede138749d57}, doi = {10.3390/gels9090765}, issn = {23102861}, year = {2023}, date = {2023-09-20}, journal = {Gels}, volume = {9}, number = {9}, pages = {765}, abstract = {A cryogel is a cross-linked polymer network with different properties that are determined by its manufacturing technique. The formation of a cryogel occurs at low temperatures and results in a porous structure whose pore size is affected by thermal conditions. The adjustable pore sizes of cryogels make them attractive for diverse applications. In this study, the influence of the external operational temperature, which affects the cooling and freezing rates, on the production of cryogels with 2% w/w agarose is investigated. Moreover, a mathematical model is developed to simulate the cryogel production process and provide an initial estimate of the pore size within the structure. The predictions of the model, supported by qualitative light microscopy images, demonstrate that cryogels produced at higher process temperatures exhibit larger pore sizes. Moreover, the existence of pore size distribution within the gel structure is confirmed. Finally, stress relaxation tests, coupled with an image analysis, validates that cryogels produced at lower temperatures possess a higher stiffness and slower water release rates.}, keywords = {Agarose, cryogels, Equilibrium, Hydrogels, Modeling, Rheology}, pubstate = {published}, tppubtype = {article} } A cryogel is a cross-linked polymer network with different properties that are determined by its manufacturing technique. The formation of a cryogel occurs at low temperatures and results in a porous structure whose pore size is affected by thermal conditions. The adjustable pore sizes of cryogels make them attractive for diverse applications. In this study, the influence of the external operational temperature, which affects the cooling and freezing rates, on the production of cryogels with 2% w/w agarose is investigated. Moreover, a mathematical model is developed to simulate the cryogel production process and provide an initial estimate of the pore size within the structure. The predictions of the model, supported by qualitative light microscopy images, demonstrate that cryogels produced at higher process temperatures exhibit larger pore sizes. Moreover, the existence of pore size distribution within the gel structure is confirmed. Finally, stress relaxation tests, coupled with an image analysis, validates that cryogels produced at lower temperatures possess a higher stiffness and slower water release rates. |
Caccavo, Diego; Iannone, Marco; Barba, Anna Angela; Lamberti, Gaetano Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets Journal Article Chemical Engineering Science, 267 , 2023. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, Mathematical modeling, Pharmacokinetics @article{Caccavo2023, title = {Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets}, author = {Diego Caccavo and Marco Iannone and Anna Angela Barba and Gaetano Lamberti}, url = {https://www.sciencedirect.com/science/article/pii/S0009250922009563}, doi = {10.1016/j.ces.2022.118371}, year = {2023}, date = {2023-03-05}, journal = {Chemical Engineering Science}, volume = {267}, abstract = {The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behavior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration.}, keywords = {Drug Delivery Systems, Mathematical modeling, Pharmacokinetics}, pubstate = {published}, tppubtype = {article} } The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behavior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration. |
2022 |
Caccavo, Diego; Della Vecchia, Marica ; Barba, Anna Angela; Lamberti, Gaetano Simil-microfluidic ethanol injection mixer for the continuous synthesis production of liposomes: laminar vs turbulent regime Inproceedings CHISA - Prague (Czech Republic), 2022. BibTeX | Tags: Drug Delivery Systems, Micro and Nano Vectors @inproceedings{Caccavo2022, title = {Simil-microfluidic ethanol injection mixer for the continuous synthesis production of liposomes: laminar vs turbulent regime}, author = {Diego Caccavo and Marica {Della Vecchia} and Anna Angela Barba and Gaetano Lamberti}, year = {2022}, date = {2022-08-23}, booktitle = {CHISA - Prague (Czech Republic)}, keywords = {Drug Delivery Systems, Micro and Nano Vectors}, pubstate = {published}, tppubtype = {inproceedings} } |
De Piano, Raffaella ; Caccavo, Diego; Barba, Anna Angela; Lamberti, Gaetano Anionic hydrogels: equilibrium behaviour modelling Inproceedings CHISA - Prague (Czech Republic), 2022. BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @inproceedings{Piano}2022, title = {Anionic hydrogels: equilibrium behaviour modelling}, author = {Raffaella {De Piano} and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti}, year = {2022}, date = {2022-08-23}, booktitle = {CHISA - Prague (Czech Republic)}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {inproceedings} } |
Iannone, Marco; Caccavo, Diego; Barba, Anna Angela; Lamberti, Gaetano A low-cost push–pull syringe pump for continuous flow applications Journal Article HardwareX, 11 , 2022. Abstract | Links | BibTeX | Tags: Instrumentation and control, New devices, Prototyping @article{Iannone2022, title = {A low-cost push\textendashpull syringe pump for continuous flow applications}, author = {Marco Iannone and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti}, url = {https://www.sciencedirect.com/science/article/pii/S2468067222000402}, doi = {10.1016/j.ohx.2022.e00295}, year = {2022}, date = {2022-04-01}, journal = {HardwareX}, volume = {11}, abstract = {Syringe pumps are very useful tools to ensure a constant and pulsation-free flow rate, however usability is limited to batch processes. This article shows an open-source method for manufacturing a push pull syringe pump, valid for continuous processes, easy to build, low-cost and programmable. The push\textendashpull syringe pump (PPSP) is driven by an Arduino nano ATmega328P which controls a NEMA 17 in microstepping via the A4988 stepper driver. The Push-Pull Syringe Pump setup is configurable by means of a digital encoder and an oled screen programmed using C ++. A PCB was designed and built to facilitate the assembly of the device. The continuous flow is guaranteed by four non-return valves and a dampener, which has been sized and optimized for use on this device. Finally, tests were carried out to evaluate the flow rates and the linearity of the flow. The device is achievable with a cost of less than 100 €.}, keywords = {Instrumentation and control, New devices, Prototyping}, pubstate = {published}, tppubtype = {article} } Syringe pumps are very useful tools to ensure a constant and pulsation-free flow rate, however usability is limited to batch processes. This article shows an open-source method for manufacturing a push pull syringe pump, valid for continuous processes, easy to build, low-cost and programmable. The push–pull syringe pump (PPSP) is driven by an Arduino nano ATmega328P which controls a NEMA 17 in microstepping via the A4988 stepper driver. The Push-Pull Syringe Pump setup is configurable by means of a digital encoder and an oled screen programmed using C ++. A PCB was designed and built to facilitate the assembly of the device. The continuous flow is guaranteed by four non-return valves and a dampener, which has been sized and optimized for use on this device. Finally, tests were carried out to evaluate the flow rates and the linearity of the flow. The device is achievable with a cost of less than 100 €. |
2021 |
Yu, Xu-Dong; Li, Jia-Hui; Li, Heng; Huang, Ju; Caccavo, Diego; Lamberti, Gaetano; Chu, Li-Qiang Gelation process of carboxymethyl chitosan-zinc supramolecular hydrogel studied with fluorescence imaging and mathematical modelling Journal Article International Journal of Pharmaceutics, 2021. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @article{Yu2021, title = {Gelation process of carboxymethyl chitosan-zinc supramolecular hydrogel studied with fluorescence imaging and mathematical modelling}, author = {Xu-Dong Yu and Jia-Hui Li and Heng Li and Ju Huang and Diego Caccavo and Gaetano Lamberti and Li-Qiang Chu }, url = {https://www.sciencedirect.com/science/article/pii/S0378517321006098}, doi = {10.1016/j.ijpharm.2021.120804}, year = {2021}, date = {2021-06-16}, journal = {International Journal of Pharmaceutics}, abstract = {Herein we report on a detailed study about the gelation kinetics of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel by taking advantage of its intrinsic fluorescence property. A specific gelation device is designed and the gel front can be directly visualized under 365 nm UV light. The results show that when increasing Zn2+ concentration from 0.1 M to 1.0 M, the apparent diffusion coefficient increases gradually from 2.72×10-6 cm2/s to 4.50×10-6 cm2/s. The gelation kinetics then is described with a “zero order” mathematical model, proving that the gel thickness is related to the square root of the gelation time and the diffusion step is the controlling step of the gelation process. Later a more advanced model, developed in 1D geometry and solved numerically, is used to describe and predict experimental results, proving its reliability and the correct description of all the phenomena involved in the gelation process of CMCh-Zn hydrogel.}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Herein we report on a detailed study about the gelation kinetics of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel by taking advantage of its intrinsic fluorescence property. A specific gelation device is designed and the gel front can be directly visualized under 365 nm UV light. The results show that when increasing Zn2+ concentration from 0.1 M to 1.0 M, the apparent diffusion coefficient increases gradually from 2.72×10-6 cm2/s to 4.50×10-6 cm2/s. The gelation kinetics then is described with a “zero order” mathematical model, proving that the gel thickness is related to the square root of the gelation time and the diffusion step is the controlling step of the gelation process. Later a more advanced model, developed in 1D geometry and solved numerically, is used to describe and predict experimental results, proving its reliability and the correct description of all the phenomena involved in the gelation process of CMCh-Zn hydrogel. |
Caccavo, Diego; Cavallo, Rosario; Abrami, Michela; Grassi, Mario; Barba, Anna Angela; Lamberti, Gaetano Dynamometric measurements of hydrogels' mechanical spectra Journal Article Journal of Applied Polymer Science, 2021. Abstract | Links | BibTeX | Tags: Gels, Rheology, Viscosity and Viscoelasticity @article{Caccavo2021, title = {Dynamometric measurements of hydrogels' mechanical spectra}, author = {Diego Caccavo and Rosario Cavallo and Michela Abrami and Mario Grassi and Anna Angela Barba and Gaetano Lamberti}, url = {https://onlinelibrary.wiley.com/doi/full/10.1002/app.50702}, doi = {10.1002/app.50702}, year = {2021}, date = {2021-03-12}, journal = {Journal of Applied Polymer Science}, abstract = {Hydrogels' viscoelastic behavior is crucial in several applications and an in‐depth knowledge and characterization of this property is essential to select the most appropriate gel for the specific use. Oscillatory shear measurements are the most commonly used techniques to perform the viscoelastic characterization of hydrogels, among other materials, and it is performed mainly by using plate‐plate shear rheometers. Despite these instruments constitute one of the best options to analyze the mechanical response of materials, they are quite expensive and require well trained operators, which confine their presence exclusively in engineering labs. However, the use of hydrogels brought these materials to be present in countless sectors, and therefore poses the need of reliable characterization with as much simple and common instrumentations. Therefore, aim of this work is to present the possibility to obtain a trustworthy characterization of the viscoelasticity of hydrogel by using a Texture Analyzer set to work with sinusoidal deformations.}, keywords = {Gels, Rheology, Viscosity and Viscoelasticity}, pubstate = {published}, tppubtype = {article} } Hydrogels' viscoelastic behavior is crucial in several applications and an in‐depth knowledge and characterization of this property is essential to select the most appropriate gel for the specific use. Oscillatory shear measurements are the most commonly used techniques to perform the viscoelastic characterization of hydrogels, among other materials, and it is performed mainly by using plate‐plate shear rheometers. Despite these instruments constitute one of the best options to analyze the mechanical response of materials, they are quite expensive and require well trained operators, which confine their presence exclusively in engineering labs. However, the use of hydrogels brought these materials to be present in countless sectors, and therefore poses the need of reliable characterization with as much simple and common instrumentations. Therefore, aim of this work is to present the possibility to obtain a trustworthy characterization of the viscoelasticity of hydrogel by using a Texture Analyzer set to work with sinusoidal deformations. |
2020 |
De Piano, Raffaella ; Caccavo, Diego; Cascone, Sara; Festa, Caterina; Lamberti, Gaetano; Barba, Anna Angela Drug release from hydrogel-based matrix systems partially coated: experiments and modeling Journal Article Journal of Drug Delivery Science and Technology, 2020. Abstract | Links | BibTeX | Tags: drug release, Modeling, Tablets, Theophylline @article{Piano}2020, title = {Drug release from hydrogel-based matrix systems partially coated: experiments and modeling}, author = {Raffaella {De Piano} and Diego Caccavo and Sara Cascone and Caterina Festa and Gaetano Lamberti and Anna Angela Barba}, url = {https://www.sciencedirect.com/science/article/abs/pii/S1773224720314350?via%3Dihub}, doi = {10.1016/j.jddst.2020.102146}, year = {2020}, date = {2020-10-07}, journal = {Journal of Drug Delivery Science and Technology}, abstract = {Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics.}, keywords = {drug release, Modeling, Tablets, Theophylline}, pubstate = {published}, tppubtype = {article} } Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics. |
De Simone, Veronica ; Dalmoro, Annalisa; Bochicchio, Sabrina; Caccavo, Diego; Lamberti, Gaetano; Bertoncin, Paolo; Barba, Anna Angela Nanoliposomes in polymeric granules: Novel process strategy to produce stable and versatile delivery systems Journal Article Journal of Drug Delivery Science and Technology, 59 , pp. 7, 2020. Abstract | Links | BibTeX | Tags: Compressibility index, Lipid-polymeric, Simil-microfluidic method, Texture analyses, Wet granulation @article{Simone}2020b, title = {Nanoliposomes in polymeric granules: Novel process strategy to produce stable and versatile delivery systems}, author = {Veronica {De Simone} and Annalisa Dalmoro and Sabrina Bochicchio and Diego Caccavo and Gaetano Lamberti and Paolo Bertoncin and Anna Angela Barba}, url = {https://www.sciencedirect.com/science/article/abs/pii/S1773224720311679?via%3Dihub}, doi = {10.1016/j.jddst.2020.101878}, year = {2020}, date = {2020-07-09}, journal = {Journal of Drug Delivery Science and Technology}, volume = {59}, pages = {7}, abstract = {Liposomes, due to their mimetic cellular composition, are gaining great attention as release systems for lipophilic and hydrophilic molecules. However, liposomes can present a high tendency to degrade and aggregate into biological fluids and under storage conditions. To overcome these limitations, in this work, a stabilizing strategy consisting in liposomes incorporation into polymeric granules was studied. Wet granulation was adopted to produce granules of hydroxypropyl methylcellulose (HPMC) and liposomal suspensions were used as the binder phase. In particular, in this study, three different percentages of liposome load in HPMC granules were investigated (1%, 5% and 10% w/w) focusing the attention on several relevant technological characteristics of the achieved solid particulates: size, flow index, mechanical strength (granules without liposomal inclusions were used as a control). Morphological observations (by TEM) confirmed the presence of intact liposomes in dry HPMC granules; moreover, it was found that the binder phase with the lower liposome concentrations (1%, 5%) did not significantly affect size, flowability and hardness of the lipid-polymer granules. Instead, the granules containing the highest percentage of liposomes (10% w/w) have larger dimensions, harder structure and reduced flowability. Therefore, the followed process strategy, under liposomal concentration restrictions, allowed to obtain both the liposomes stabilization, a not trivial technological issue, and the production of particulates with good solid state properties, useful as a versatile dosage form (lipid carriers in polymer carriers).}, keywords = {Compressibility index, Lipid-polymeric, Simil-microfluidic method, Texture analyses, Wet granulation}, pubstate = {published}, tppubtype = {article} } Liposomes, due to their mimetic cellular composition, are gaining great attention as release systems for lipophilic and hydrophilic molecules. However, liposomes can present a high tendency to degrade and aggregate into biological fluids and under storage conditions. To overcome these limitations, in this work, a stabilizing strategy consisting in liposomes incorporation into polymeric granules was studied. Wet granulation was adopted to produce granules of hydroxypropyl methylcellulose (HPMC) and liposomal suspensions were used as the binder phase. In particular, in this study, three different percentages of liposome load in HPMC granules were investigated (1%, 5% and 10% w/w) focusing the attention on several relevant technological characteristics of the achieved solid particulates: size, flow index, mechanical strength (granules without liposomal inclusions were used as a control). Morphological observations (by TEM) confirmed the presence of intact liposomes in dry HPMC granules; moreover, it was found that the binder phase with the lower liposome concentrations (1%, 5%) did not significantly affect size, flowability and hardness of the lipid-polymer granules. Instead, the granules containing the highest percentage of liposomes (10% w/w) have larger dimensions, harder structure and reduced flowability. Therefore, the followed process strategy, under liposomal concentration restrictions, allowed to obtain both the liposomes stabilization, a not trivial technological issue, and the production of particulates with good solid state properties, useful as a versatile dosage form (lipid carriers in polymer carriers). |
Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela Mechanics and drug release from poroviscoelastic hydrogels: Experiments and modeling Journal Article European Journal of Pharmaceutics and Biopharmaceutics, 152 , pp. 299-306, 2020. Abstract | Links | BibTeX | Tags: Agarose, drug delivery, Hydrogels, Modeling, Poroviscoelasticity @article{Caccavo2020, title = {Mechanics and drug release from poroviscoelastic hydrogels: Experiments and modeling}, author = {Diego Caccavo and Gaetano Lamberti and Anna Angela Barba}, url = {https://doi.org/10.1016/j.ejpb.2020.05.020}, doi = {10.1016/j.ejpb.2020.05.020}, year = {2020}, date = {2020-05-27}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {152}, pages = {299-306}, abstract = {Hydrogels are peculiar soft materials formed by a 3D polymeric network surrounded by water molecules. In these systems the mechanical and the chemical energy are well balanced and an applied external stimulus (mechanical or chemical) can cause a distinctive response, where the contributions of the mechanics and the mass transport are combined to form a “poroviscoelastic” behavior. In this work the poroviscoelastic behavior of the agarose gels has been investigated, from the experimental and modeling points of view, by applications of external mechanical stimuli. The pure gel, brought in the non-equilibrium condition, showed that the combined effect of mechanical viscoelasticity and water transport were essential to reach the new equilibrium condition. Furthermore, the agarose gel loaded with a model drug, theophylline, showed that the mechanical stimulus can enhance the drug release from the system by stretching the polymeric chains, modifying the mesh size and therefore the drug diffusion coefficient.}, keywords = {Agarose, drug delivery, Hydrogels, Modeling, Poroviscoelasticity}, pubstate = {published}, tppubtype = {article} } Hydrogels are peculiar soft materials formed by a 3D polymeric network surrounded by water molecules. In these systems the mechanical and the chemical energy are well balanced and an applied external stimulus (mechanical or chemical) can cause a distinctive response, where the contributions of the mechanics and the mass transport are combined to form a “poroviscoelastic” behavior. In this work the poroviscoelastic behavior of the agarose gels has been investigated, from the experimental and modeling points of view, by applications of external mechanical stimuli. The pure gel, brought in the non-equilibrium condition, showed that the combined effect of mechanical viscoelasticity and water transport were essential to reach the new equilibrium condition. Furthermore, the agarose gel loaded with a model drug, theophylline, showed that the mechanical stimulus can enhance the drug release from the system by stretching the polymeric chains, modifying the mesh size and therefore the drug diffusion coefficient. |
Barba, Anna Angela; Dalmoro, Annalisa; Bochicchio, Sabrina; Simone, Veronica De; Caccavo, Diego; Iannone, Marco; Lamberti, Gaetano Engineering approaches for drug delivery systems production and characterization Journal Article International Journal of Pharmaceutics, 2020. Abstract | Links | BibTeX | Tags: drug delivery, Hydrogel, Innovation in Europe, Microvectors, Modeling, Nanovectors @article{Barba2020, title = {Engineering approaches for drug delivery systems production and characterization}, author = {Anna Angela Barba and Annalisa Dalmoro and Sabrina Bochicchio and Veronica De Simone and Diego Caccavo and Marco Iannone and Gaetano Lamberti}, url = {https://www.sciencedirect.com/science/article/pii/S0378517320302519}, doi = {10.1016/j.ijpharm.2020.119267}, year = {2020}, date = {2020-03-31}, journal = {International Journal of Pharmaceutics}, abstract = {To find and to test the therapeutic effectiveness (and the limited adverse effects) of a new drug is a long and expensive process. It has been estimated a period of ten years and an expense of the order of one billion USD are required. Meanwhile, even if a promising molecule has been identified, there is the need for operative methods for its delivery. The extreme case is given by gene therapy, in which molecules with tremendous in-vitro efficacy cannot be used in practice because of the lack in useful vector systems to deliver them. Most of the recent efforts in pharmaceutical sciences are focused on the development of novel drug delivery systems (DDSs). In this review, the work done recently on the development and testing of novel DDSs, with particular emphasis on the results obtained by European research, is summarized. In the first section of the review the DDSs are analyzed accordingly with their scale-size: starting from nano-scale (liposomes, nanoparticles), up to the micro-scale (microparticles), until the macroscopic world is reached (granules, matrix systems). In the following two sections, non-conventional testing methods (mechanical methods and bio-relevant dissolution methods) are presented; at last, the importance of mathematical modeling to describe drug release and related phenomena is reported.}, keywords = {drug delivery, Hydrogel, Innovation in Europe, Microvectors, Modeling, Nanovectors}, pubstate = {published}, tppubtype = {article} } To find and to test the therapeutic effectiveness (and the limited adverse effects) of a new drug is a long and expensive process. It has been estimated a period of ten years and an expense of the order of one billion USD are required. Meanwhile, even if a promising molecule has been identified, there is the need for operative methods for its delivery. The extreme case is given by gene therapy, in which molecules with tremendous in-vitro efficacy cannot be used in practice because of the lack in useful vector systems to deliver them. Most of the recent efforts in pharmaceutical sciences are focused on the development of novel drug delivery systems (DDSs). In this review, the work done recently on the development and testing of novel DDSs, with particular emphasis on the results obtained by European research, is summarized. In the first section of the review the DDSs are analyzed accordingly with their scale-size: starting from nano-scale (liposomes, nanoparticles), up to the micro-scale (microparticles), until the macroscopic world is reached (granules, matrix systems). In the following two sections, non-conventional testing methods (mechanical methods and bio-relevant dissolution methods) are presented; at last, the importance of mathematical modeling to describe drug release and related phenomena is reported. |
2019 |
Barba, Anna Angela; Bochicchio, Sabrina; Dalmoro, Annalisa; Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano Polymeric and lipid-based systems for controlled drug release: an engineering point of view Book Chapter Grumezescu, Alexandru Mihai (Ed.): Chapter 10, pp. 267-304, Elsevier, 2019, ISBN: 978-0-12-816505-8. Abstract | Links | BibTeX | Tags: characterization techniques, controlled release, lipid nanoparticles, Mathematical modeling, Polymer nanoparticles, production processes @inbook{Barba2019c, title = {Polymeric and lipid-based systems for controlled drug release: an engineering point of view}, author = {Anna Angela Barba and Sabrina Bochicchio and Annalisa Dalmoro and Diego Caccavo and Sara Cascone and Gaetano Lamberti}, editor = {Alexandru Mihai Grumezescu}, url = {https://www.sciencedirect.com/science/article/pii/B9780128165058000138?via%3Dihub#kys0010}, doi = {10.1016/B978-0-12-816505-8.00013-8}, isbn = {978-0-12-816505-8}, year = {2019}, date = {2019-12-02}, pages = {267-304}, publisher = {Elsevier}, chapter = {10}, abstract = {Aim of this chapter is to review the most common techniques to produce and to characterize systems for controlled drug release, giving particular emphasis to the fundamentals of the production processes and to the possibility to describe mathematically the phenomena involved in drug release, that is, looking at the processes from an engineering point of view. The most commonly used materials are briefly reviewed, both the polymeric materials (preformed and ad-hoc synthetized, natural, and synthetic) as well as the lipid materials. Then, the drug delivery systems’ preparation processes are presented and discussed. Particular focus is given to the preparation of micro- and nanoparticles based on preformed polymers, and to preparation processes for liposomes. Advanced characterization techniques for novel and conventional drug delivery systems are then presented. Last but not least, the most modern modeling approaches to describe the drug release from these drug delivery systems are reported and compared.}, keywords = {characterization techniques, controlled release, lipid nanoparticles, Mathematical modeling, Polymer nanoparticles, production processes}, pubstate = {published}, tppubtype = {inbook} } Aim of this chapter is to review the most common techniques to produce and to characterize systems for controlled drug release, giving particular emphasis to the fundamentals of the production processes and to the possibility to describe mathematically the phenomena involved in drug release, that is, looking at the processes from an engineering point of view. The most commonly used materials are briefly reviewed, both the polymeric materials (preformed and ad-hoc synthetized, natural, and synthetic) as well as the lipid materials. Then, the drug delivery systems’ preparation processes are presented and discussed. Particular focus is given to the preparation of micro- and nanoparticles based on preformed polymers, and to preparation processes for liposomes. Advanced characterization techniques for novel and conventional drug delivery systems are then presented. Last but not least, the most modern modeling approaches to describe the drug release from these drug delivery systems are reported and compared. |
Caccavo, Diego An overview on the mathematical modeling of hydrogels’ behavior for drug delivery systems Journal Article International Journal of Pharmaceutics, 560 , pp. 175-190, 2019. Abstract | Links | BibTeX | Tags: Hydrogel Modeling @article{Caccavo2019, title = {An overview on the mathematical modeling of hydrogels’ behavior for drug delivery systems}, author = {Diego Caccavo}, url = {https://www.sciencedirect.com/science/article/pii/S0378517319301188?via%3Dihub}, doi = {10.1016/j.ijpharm.2019.01.076}, year = {2019}, date = {2019-02-11}, journal = {International Journal of Pharmaceutics}, volume = {560}, pages = {175-190}, abstract = {Hydrogels-based systems (HBSs) for drug delivery are nowadays extensively used and the interest in modeling their behavior is dramatically increasing. In this review a critical overview on the modeling approaches is given, quantitatively and qualitatively analyzing the publications on the subject, the trend of the publications per year and the type of modeling approaches. It was found that, despite the drug release fitting models (i.e. Higuchi’s equation) are the most abundant, their use for HBSs is decreasing in the last years and luckily, considering the limiting assumption on which they were built, they will be confined to simple mathematical fitting equations. Within the mechanistic models the “multi-component” with the swelling approximation (mass transport only) and with the mechanics (fully coupled) are experiencing the highest growth rate, with much more interest toward the last one that, in the next years could be able to provide a first principles model. Statistical models, especially based on the response surface methodology, are rapidly spreading in the scientific community mainly thanks to their ability to be predictive, regardless of the phenomenology, in the analyzed design space with very low efforts. Neural Networks models for HBSs, in countertrend with their use in the pharmaceutical industry, have never take off preferring less data demanding statistical models.}, keywords = {Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels-based systems (HBSs) for drug delivery are nowadays extensively used and the interest in modeling their behavior is dramatically increasing. In this review a critical overview on the modeling approaches is given, quantitatively and qualitatively analyzing the publications on the subject, the trend of the publications per year and the type of modeling approaches. It was found that, despite the drug release fitting models (i.e. Higuchi’s equation) are the most abundant, their use for HBSs is decreasing in the last years and luckily, considering the limiting assumption on which they were built, they will be confined to simple mathematical fitting equations. Within the mechanistic models the “multi-component” with the swelling approximation (mass transport only) and with the mechanics (fully coupled) are experiencing the highest growth rate, with much more interest toward the last one that, in the next years could be able to provide a first principles model. Statistical models, especially based on the response surface methodology, are rapidly spreading in the scientific community mainly thanks to their ability to be predictive, regardless of the phenomenology, in the analyzed design space with very low efforts. Neural Networks models for HBSs, in countertrend with their use in the pharmaceutical industry, have never take off preferring less data demanding statistical models. |
De Simone, Veronica ; Dalmoro, Annalisa; Lamberti, Gaetano; Caccavo, Diego; D'Amore, Matteo; Barba, Anna Angela Effect of binder and load solubility properties on HPMC granules produced by wet granulation process Journal Article Journal of Drug Delivery Science and Technology, 49 , pp. 513-520, 2019. Abstract | Links | BibTeX | Tags: Granulation, HPMC @article{Simone}2019, title = {Effect of binder and load solubility properties on HPMC granules produced by wet granulation process}, author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba}, url = {https://www.sciencedirect.com/science/article/pii/S1773224718311043}, doi = {10.1016/j.jddst.2018.12.030}, year = {2019}, date = {2019-02-01}, journal = {Journal of Drug Delivery Science and Technology}, volume = {49}, pages = {513-520}, abstract = {Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.}, keywords = {Granulation, HPMC}, pubstate = {published}, tppubtype = {article} } Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively. |
2018 |
De Simone, Veronica ; Caccavo, Diego; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela Wet-granulation process: phenomenological analysis and process parameters optimization Journal Article Powder Technology, 340 , pp. 411-419, 2018. Abstract | Links | BibTeX | Tags: Granulation, HPMC @article{Simone}2018b, title = {Wet-granulation process: phenomenological analysis and process parameters optimization}, author = {Veronica {De Simone} and Diego Caccavo and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba}, url = {https://www.sciencedirect.com/science/article/pii/S0032591018307800}, doi = {10.1016/j.powtec.2018.09.053}, year = {2018}, date = {2018-12-01}, journal = {Powder Technology}, volume = {340}, pages = {411-419}, abstract = {Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000\textendash10,000 μm) as the main variable of interest.}, keywords = {Granulation, HPMC}, pubstate = {published}, tppubtype = {article} } Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000–10,000 μm) as the main variable of interest. |
De Simone, Veronica ; Caccavo, Diego; Dalmoro, Annalisa; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters Book Chapter Kyzas, George (Ed.): Chapter 5, IntechOpen, 2018, ISBN: 978-1-78984-308-8. Abstract | Links | BibTeX | Tags: Granulation, HPMC, Mathematical modeling @inbook{Simone}2018c, title = {Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters}, author = {Veronica {De Simone} and Diego Caccavo and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba}, editor = {George Kyzas}, url = {https://www.intechopen.com/books/granularity-in-materials-science/inside-the-phenomenological-aspects-of-wet-granulation-role-of-process-parameters}, doi = {10.5772/intechopen.79840}, isbn = {978-1-78984-308-8}, year = {2018}, date = {2018-10-24}, publisher = {IntechOpen}, chapter = {5}, abstract = {Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed.}, keywords = {Granulation, HPMC, Mathematical modeling}, pubstate = {published}, tppubtype = {inbook} } Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed. |
Caccavo, Diego; Vietri, Antonella; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette Modeling the mechanics and the transport phenomena in hydrogels Book Chapter Manca, Davide (Ed.): Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications, Chapter 12, 2018. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @inbook{Caccavo2018b, title = {Modeling the mechanics and the transport phenomena in hydrogels}, author = {Diego Caccavo and Antonella Vietri and Gaetano Lamberti and Anna Angela Barba and Anette Larsson }, editor = {Davide Manca}, url = {https://www.sciencedirect.com/science/article/pii/B978044463964600012X}, doi = {10.1016/B978-0-444-63964-6.00012-X}, year = {2018}, date = {2018-07-18}, booktitle = {Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications}, chapter = {12}, abstract = {Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as\textemdashin principle\textemdashany other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters).}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {inbook} } Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as—in principle—any other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters). |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour Journal Article Chemical Society Reviews, 47 (7), pp. 2357-2373, 2018, ISSN: 0306-0012. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @article{Caccavo2018, title = {Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour}, author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba}, url = {http://pubs.rsc.org/en/content/articlelanding/2018/cs/c7cs00638a#!divAbstract}, doi = {10.1039/C7CS00638A}, issn = {0306-0012}, year = {2018}, date = {2018-04-07}, journal = {Chemical Society Reviews}, volume = {47}, number = {7}, pages = {2357-2373}, abstract = {Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure\textendashproperty relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure–property relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented. |
De Simone, Veronica ; Dalmoro, Annalisa; Lamberti, Gaetano; Caccavo, Diego; D'Amore, Matteo; Barba, Anna Angela HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties Journal Article Carbohydrate Polymers, 181 , pp. 939-947, 2018. Abstract | Links | BibTeX | Tags: Granulation @article{{DeSimone}2018, title = {HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties}, author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba }, url = {http://www.sciencedirect.com/science/article/pii/S0144861717313425}, doi = {10.1016/j.carbpol.2017.11.056}, year = {2018}, date = {2018-02-01}, journal = {Carbohydrate Polymers}, volume = {181}, pages = {939-947}, abstract = {Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45\textendash2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45\textendash2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.}, keywords = {Granulation}, pubstate = {published}, tppubtype = {article} } Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45–2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45–2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation. |
2017 |
Caccavo, Diego; Barba, Anna Angela; D'Amore, Matteo; De Piano, Raffaella ; Lamberti, Gaetano; Rossi, Alessandra; Colombo, Paolo Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix® Journal Article European Journal of Pharmaceutics and Biopharmaceutics, 121 , pp. 24-31, 2017, ISSN: 0939-6411. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @article{Caccavo2017b, title = {Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®}, author = {Diego Caccavo and Anna Angela Barba and Matteo D'Amore and Raffaella {De Piano} and Gaetano Lamberti and Alessandra Rossi and Paolo Colombo}, url = {http://www.sciencedirect.com/science/article/pii/S0939641117308366}, doi = {10.1016/j.ejpb.2017.08.016}, issn = {0939-6411}, year = {2017}, date = {2017-12-01}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {121}, pages = {24-31}, abstract = {The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. |
Caccavo, Diego; Cascone, Sara; Apicella, Pietro; Lamberti, Gaetano; Barba, Anna Angela HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture Journal Article Chemical Engineering Communications, 204 (12), pp. 1333-1340, 2017, ISSN: 0098-6445. Abstract | Links | BibTeX | Tags: Granulation, HPMC @article{Caccavo2017b, title = {HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture}, author = {Diego Caccavo and Sara Cascone and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba}, url = {http://www.tandfonline.com/doi/full/10.1080/00986445.2017.1362398}, doi = {10.1080/00986445.2017.1362398 }, issn = {0098-6445}, year = {2017}, date = {2017-12-01}, journal = {Chemical Engineering Communications}, volume = {204}, number = {12}, pages = {1333-1340}, abstract = {One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.}, keywords = {Granulation, HPMC}, pubstate = {published}, tppubtype = {article} } One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices. |
Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Abrahmsén-Alami, Susanna; Viridén, Anna; Larsson, Anette Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study Journal Article International Journal of Pharmaceutics, 528 (1-2), pp. 705-713, 2017, ISSN: 0378-5173. Abstract | Links | BibTeX | Tags: Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Mathematical modeling @article{Larsson2017, title = {Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study}, author = {Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Susanna Abrahms\'{e}n-Alami and Anna Virid\'{e}n and Anette Larsson}, url = {http://www.sciencedirect.com/science/article/pii/S0378517317305720}, doi = {10.1016/j.ijpharm.2017.06.064}, issn = {0378-5173}, year = {2017}, date = {2017-08-07}, journal = {International Journal of Pharmaceutics}, volume = {528}, number = {1-2}, pages = {705-713}, abstract = {The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices. }, keywords = {Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Mathematical modeling}, pubstate = {published}, tppubtype = {article} } The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices. |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Dalmoro, Annalisa; Barba, Anna Angela Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications Journal Article Natural Product Communications, 12 (6), pp. 867-871, 2017, ISSN: 1934-578X. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Mathematical modeling, Modeling @article{NPC02, title = {Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications}, author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Annalisa Dalmoro and Anna Angela Barba}, url = {http://www.naturalproduct.us/index.asp https://www.gruppotpp.it/wp-content/uploads/2017/06/Caccavo-et-al-NPC-126-867-871-2017-Abstract.pdf}, issn = {1934-578X}, year = {2017}, date = {2017-07-31}, journal = {Natural Product Communications}, volume = {12}, number = {6}, pages = {867-871}, abstract = {Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources. In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications. }, keywords = {Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Mathematical modeling, Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources. In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications. |
Caccavo, Diego; Lamberti, Gaetano PoroViscoElastic model to describe hydrogels' behavior Journal Article Materials Science and Engineering: C, 76 , pp. 102–113, 2017. Abstract | Links | BibTeX | Tags: Hydrogel Modeling @article{Caccavo2017, title = {PoroViscoElastic model to describe hydrogels' behavior}, author = {Diego Caccavo and Gaetano Lamberti}, url = {http://www.sciencedirect.com/science/article/pii/S0928493116325760}, doi = {10.1016/j.msec.2017.02.155}, year = {2017}, date = {2017-07-01}, journal = {Materials Science and Engineering: C}, volume = {76}, pages = {102\textendash113}, abstract = {Hydrogels are three-dimensional, cross-linked hydrophilic polymeric network able of absorb large amount of water. The mechanics of these systems is strictly coupled with the water transport resulting in the peculiar behavior known as poroviscoelasticy. This can be considered as sum of the viscoelastic behavior of the polymeric network and the poroelastic behavior caused by the water movement within the hydrogel. In this work a 3D monophasic model able to depict the poroviscoelastic behavior of these systems, within the field of nonlinear solid mechanics, is developed. The mass and momentum balances equations, supported by constitutive equations from non-equilibrium thermodynamics and by initial and boundary conditions, is implemented through the weak formulation in a commercial FEM-based software. A parametric study is performed in order to assess the relative importance of the model parameters on hydrogels' behavior.}, keywords = {Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels are three-dimensional, cross-linked hydrophilic polymeric network able of absorb large amount of water. The mechanics of these systems is strictly coupled with the water transport resulting in the peculiar behavior known as poroviscoelasticy. This can be considered as sum of the viscoelastic behavior of the polymeric network and the poroelastic behavior caused by the water movement within the hydrogel. In this work a 3D monophasic model able to depict the poroviscoelastic behavior of these systems, within the field of nonlinear solid mechanics, is developed. The mass and momentum balances equations, supported by constitutive equations from non-equilibrium thermodynamics and by initial and boundary conditions, is implemented through the weak formulation in a commercial FEM-based software. A parametric study is performed in order to assess the relative importance of the model parameters on hydrogels' behavior. |
Caccavo, Diego; Cascone, Sara; Poto, Serena; Lamberti, Gaetano; Barba, Anna Angela Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests Journal Article Carbohydrate Polymers, 167 , pp. 136–144, 2017. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @article{Caccavo2017b, title = {Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests}, author = {Diego Caccavo and Sara Cascone and Serena Poto and Gaetano Lamberti and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S0144861717302837}, doi = {10.1016/j.carbpol.2017.03.027}, year = {2017}, date = {2017-07-01}, journal = {Carbohydrate Polymers}, volume = {167}, pages = {136\textendash144}, abstract = {Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels’ behavior. }, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels’ behavior. |
Barba, Anna Angela; Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Chiarappa, Gianluca; Abrami, Michela; Grassi, Gabriele; Grassi, Mario; Tomaiuolo, Giovanna; Guido, Stefano; Brucato, Valerio; Carfì Pavia, Francesco ; Ghersi, Giulio; La Carrubba, Vincenzo ; Abbiati, Roberto Andrea; Manca, Davide Engineering approaches in siRNA delivery Journal Article International Journal of Pharmaceutics, 525 (2), pp. 343–358, 2017. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Barba2017, title = {Engineering approaches in siRNA delivery}, author = {Anna Angela Barba and Sara Cascone and Diego Caccavo and Gaetano Lamberti and Gianluca Chiarappa and Michela Abrami and Gabriele Grassi and Mario Grassi and Giovanna Tomaiuolo and Stefano Guido and Valerio Brucato and Francesco {Carf\`{i} Pavia} and Giulio Ghersi and Vincenzo {La Carrubba} and Roberto Andrea Abbiati and Davide Manca}, url = {http://www.sciencedirect.com/science/article/pii/S0378517317301138}, doi = {10.1016/j.ijpharm.2017.02.032}, year = {2017}, date = {2017-06-20}, journal = {International Journal of Pharmaceutics}, volume = {525}, number = {2}, pages = {343\textendash358}, abstract = {siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors’ production processes and siRNAs vectors’ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors’ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors’ production processes and siRNAs vectors’ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors’ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications. |
Kazlauske, Jurgita; Cafaro, Maria Margherita; Caccavo, Diego; Marucci, Maria Grazia; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette Determination of the release mechanism of Theophylline from pellets coated with Surelease® − a water dispersion of Ethyl cellulose Journal Article International Journal of Pharmaceutics, 528 (1-2), pp. 345-353, 2017, ISSN: 0378-5173. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, drug release, Hydrogel Characterization @article{Kazlauske2017, title = {Determination of the release mechanism of Theophylline from pellets coated with Surelease® − a water dispersion of Ethyl cellulose}, author = {Jurgita Kazlauske and Maria Margherita Cafaro and Diego Caccavo and Maria Grazia Marucci and Gaetano Lamberti and Anna Angela Barba and Anette Larsson}, url = {http://www.sciencedirect.com/science/article/pii/S0378517317304970}, doi = {10.1016/j.ijpharm.2017.05.073}, issn = {0378-5173}, year = {2017}, date = {2017-06-17}, journal = {International Journal of Pharmaceutics}, volume = {528}, number = {1-2}, pages = {345-353}, abstract = {The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 μm) of the coating layer controlling the drug release rate.}, keywords = {Drug Delivery Systems, drug release, Hydrogel Characterization}, pubstate = {published}, tppubtype = {article} } The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 μm) of the coating layer controlling the drug release rate. |
Caccavo, Diego; Lamberti, Gaetano; Cafaro, Maria Margherita; Barba, Anna Angela; Kazlauske, Jurgita; Larsson, Anette Mathematical modeling of the drug release from an ensemble of coated pellets Journal Article British Journal of Pharmacology, 174 (12), pp. 1797–1809 , 2017, ISBN: 1476-5381. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, drug release, Hydrogel Characterization, Hydrogel Modeling @article{Caccavo2017b, title = {Mathematical modeling of the drug release from an ensemble of coated pellets}, author = {Diego Caccavo and Gaetano Lamberti and Maria Margherita Cafaro and Anna Angela Barba and Jurgita Kazlauske and Anette Larsson}, url = {http://onlinelibrary.wiley.com/doi/10.1111/bph.13776/abstract}, doi = {10.1111/bph.13776}, isbn = {1476-5381}, year = {2017}, date = {2017-04-22}, journal = {British Journal of Pharmacology}, volume = {174}, number = {12}, pages = {1797\textendash1809 }, abstract = {Background and Purpose Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models. Experimental approach In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets. Key Results In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release. Conclusions and Implications The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool.}, keywords = {Drug Delivery Systems, drug release, Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Background and Purpose Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models. Experimental approach In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets. Key Results In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release. Conclusions and Implications The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool. |
Chiarappa, Gianluca; Grassi, Mario; Abrami, Michela; Abbiati, Roberto Andrea; Barba, Anna Angela; Boisen, Anja; Brucato, Valerio; Ghersi, Giulio; Caccavo, Diego; Cascone, Sara; Caserta, Sergio; Elvassore, Nicola; Giomo, Monica; Guido, Stefano; Lamberti, Gaetano; Larobina, Domenico; Manca, Davide; Marizza, Paolo; Tomaiuolo, Giovanna; Grassi, Gabriele Chemical Engineering in the “BIO” world Journal Article Current Drug Delivery, 14 (2), pp. 158 - 178, 2017. Abstract | Links | BibTeX | Tags: @article{Chiarappa2016, title = {Chemical Engineering in the “BIO” world}, author = {Gianluca Chiarappa and Mario Grassi and Michela Abrami and Roberto Andrea Abbiati and Anna Angela Barba and Anja Boisen and Valerio Brucato and Giulio Ghersi and Diego Caccavo and Sara Cascone and Sergio Caserta and Nicola Elvassore and Monica Giomo and Stefano Guido and Gaetano Lamberti and Domenico Larobina and Davide Manca and Paolo Marizza and Giovanna Tomaiuolo and Gabriele Grassi }, url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/02.-Chiarappa-et-al-CDD-142-158-178-2017.pdf http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/158/}, doi = {10.2174/1567201813666160602230550}, year = {2017}, date = {2017-02-08}, issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY}, journal = {Current Drug Delivery}, volume = {14}, number = {2}, pages = {158 - 178}, abstract = {Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update. |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette Drug delivery from hydrogels: a general framework for the release modeling Journal Article Current Drug Delivery, 14 (2), pp. 179 - 189, 2017. Abstract | Links | BibTeX | Tags: Hydrogel Modeling @article{Caccavo2016b, title = {Drug delivery from hydrogels: a general framework for the release modeling}, author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson }, url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/03.-Caccavo-et-al-CDD-142-179-189-2017.pdf http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/179/}, doi = {10.2174/1567201813666160808102106}, year = {2017}, date = {2017-02-08}, issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY}, journal = {Current Drug Delivery}, volume = {14}, number = {2}, pages = {179 - 189}, abstract = {The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components.}, keywords = {Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components. |
2016 |
Lamberti, Gaetano; Barba, Anna Angela; Cascone, Sara; Dalmoro, Annalisa; Caccavo, Diego An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications Book Chapter Majee, Sutapa Biswas (Ed.): Emerging Concepts in Analysis and Applications of Hydrogels, Chapter 8, Intech, 2016, ISBN: 978-953-51-2510-5. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @inbook{Lamberti2016b, title = {An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications}, author = {Gaetano Lamberti and Anna Angela Barba and Sara Cascone and Annalisa Dalmoro and Diego Caccavo}, editor = {Sutapa Biswas Majee}, url = {http://www.intechopen.com/books/emerging-concepts-in-analysis-and-applications-of-hydrogels/an-engineering-point-of-view-on-the-use-of-the-hydrogels-for-pharmaceutical-and-biomedical-applicati}, doi = {10.5772/64299 }, isbn = {978-953-51-2510-5}, year = {2016}, date = {2016-08-24}, booktitle = {Emerging Concepts in Analysis and Applications of Hydrogels}, publisher = {Intech}, chapter = {8}, abstract = {In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences.}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {inbook} } In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences. |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette Swellable Hydrogel-based Systems for Controlled Drug Delivery Book Chapter Sezer, Ali Demir (Ed.): Smart Drug Delivery System, Chapter 10, Intech, 2016, ISBN: 978-953-51-2247-0. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @inbook{Caccavo2016b, title = {Swellable Hydrogel-based Systems for Controlled Drug Delivery}, author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson}, editor = {Ali Demir Sezer}, url = {http://www.intechopen.com/books/smart-drug-delivery-system/swellable-hydrogel-based-systems-for-controlled-drug-delivery#exportas}, doi = {10.5772/61792}, isbn = {978-953-51-2247-0}, year = {2016}, date = {2016-02-10}, booktitle = {Smart Drug Delivery System}, publisher = {Intech}, chapter = {10}, abstract = {The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass\textendashrubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, “eroding” the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {inbook} } The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass–rubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, “eroding” the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release. |
Caccavo, Diego; Ström, Anna; Larsson, Anette; Lamberti, Gaetano Modeling capillary formation in calcium and copper alginate gels Journal Article Materials Science and Engineering: C, 58 , pp. 442–449, 2016, ISSN: 09284931. Abstract | Links | BibTeX | Tags: Alginate, Gel capillaries, Hydrogel Characterization, Hydrogel Modeling, Ionotropic gelation, Modeling @article{Caccavo2016, title = {Modeling capillary formation in calcium and copper alginate gels}, author = { Diego Caccavo and Anna Str\"{o}m and Anette Larsson and Gaetano Lamberti}, url = {http://www.sciencedirect.com/science/article/pii/S0928493115302940}, doi = {10.1016/j.msec.2015.08.040}, issn = {09284931}, year = {2016}, date = {2016-01-01}, journal = {Materials Science and Engineering: C}, volume = {58}, pages = {442--449}, abstract = {Alginate solutions in the presence of bivalent ions can form ionic cross-linked gels. In particular gelation conditions the gel structure can be characterized by great anisotropy with the presence of straight capillaries along a preferential direction. These materials can find applications mainly in high-tech sectors, like tissue engineering, where the gel characteristics play a crucial role. Despite the need of mastering the capillary formation and properties, the process remains a poorly known problem, and its development is left to trial and error procedures. In this work a quantitative approach to the description of the capillary formation process has been developed. The theory proposed by Treml et al. (2003) has been implemented and extended to an alginate different from the one used in that study and two different ions (calcium and copper). Some of the model parameters have been derived through simple measurements; others have been scaled using proper scaling equations. Experiments have been performed in different gelation conditions, varying alginate and ionic solution concentrations, to highlight the effects of these parameters on the anisotropic structure and to validate the model. In all the analyses done, the model has performed nicely showing a good reliability in the prediction of gel characteristics like capillary formation, capillary length and process time.}, keywords = {Alginate, Gel capillaries, Hydrogel Characterization, Hydrogel Modeling, Ionotropic gelation, Modeling}, pubstate = {published}, tppubtype = {article} } Alginate solutions in the presence of bivalent ions can form ionic cross-linked gels. In particular gelation conditions the gel structure can be characterized by great anisotropy with the presence of straight capillaries along a preferential direction. These materials can find applications mainly in high-tech sectors, like tissue engineering, where the gel characteristics play a crucial role. Despite the need of mastering the capillary formation and properties, the process remains a poorly known problem, and its development is left to trial and error procedures. In this work a quantitative approach to the description of the capillary formation process has been developed. The theory proposed by Treml et al. (2003) has been implemented and extended to an alginate different from the one used in that study and two different ions (calcium and copper). Some of the model parameters have been derived through simple measurements; others have been scaled using proper scaling equations. Experiments have been performed in different gelation conditions, varying alginate and ionic solution concentrations, to highlight the effects of these parameters on the anisotropic structure and to validate the model. In all the analyses done, the model has performed nicely showing a good reliability in the prediction of gel characteristics like capillary formation, capillary length and process time. |
2015 |
Caccavo, Diego; Lamberti, Gaetano; Cascone, Sara; Barba, Anna Angela; Larsson, Anette Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment Journal Article Carbohydrate Polymers, 131 , pp. 41–49, 2015, ISSN: 01448617. Abstract | Links | BibTeX | Tags: Bio-adhesion, Carbopol, Elastic behavior, Hydrogel Characterization, Hydrogel Modeling, Modeling, Water transport @article{Caccavo2015b, title = {Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment}, author = { Diego Caccavo and Gaetano Lamberti and Sara Cascone and Anna Angela Barba and Anette Larsson}, url = {http://www.sciencedirect.com/science/article/pii/S0144861715004476}, doi = {10.1016/j.carbpol.2015.05.041}, issn = {01448617}, year = {2015}, date = {2015-10-01}, journal = {Carbohydrate Polymers}, volume = {131}, pages = {41--49}, abstract = {The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.}, keywords = {Bio-adhesion, Carbopol, Elastic behavior, Hydrogel Characterization, Hydrogel Modeling, Modeling, Water transport}, pubstate = {published}, tppubtype = {article} } The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic. |
Abrahmsén-Alami, Susanna; Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Viridén, Anna; Larsson, Anette Hydrogel-based drug delivery systems (HB-DDSs): a combined experimental-modeling approach Journal Article AstraZeneca Internal Journal, pp. 1-2, 2015. Abstract | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @article{Abrahms\'{e}n-Alami2015, title = {Hydrogel-based drug delivery systems (HB-DDSs): a combined experimental-modeling approach}, author = {Susanna Abrahms\'{e}n-Alami and Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Anna Virid\'{e}n and Anette Larsson}, year = {2015}, date = {2015-09-01}, journal = {AstraZeneca Internal Journal}, pages = {1-2}, abstract = {In this work, a method based on MR image analysis, already used to quantify the water content in hydrating tablets based on hydrogels, was refined and it was proved to be a powerful source of detailed information: the water contents were obtained as function of position and time for commercial-like tablets based on HPMC, along with the tablets’ shape changes with time, and the drug release kinetics. A mechanistic model, based on transient mass balances and surface deformation due to the hydration and erosion, previously developed and tuned, was thus applied to describe the observed phenomena, giving good results. Both the experimental technique and the mechanistic model have confirmed to be useful tools for the study of the behavior \textendash as well as for the design \textendash of the tablets based on hydrogels.}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } In this work, a method based on MR image analysis, already used to quantify the water content in hydrating tablets based on hydrogels, was refined and it was proved to be a powerful source of detailed information: the water contents were obtained as function of position and time for commercial-like tablets based on HPMC, along with the tablets’ shape changes with time, and the drug release kinetics. A mechanistic model, based on transient mass balances and surface deformation due to the hydration and erosion, previously developed and tuned, was thus applied to describe the observed phenomena, giving good results. Both the experimental technique and the mechanistic model have confirmed to be useful tools for the study of the behavior – as well as for the design – of the tablets based on hydrogels. |
Caccavo, Diego; Cascone, Sara; Bochicchio, Sabrina; Lamberti, Gaetano; Dalmoro, Annalisa; Barba, Anna Angela Hydrogels-based matrices behavior: experimental and modeling description Inproceedings 42nd Annual Meeting & Exposition of the Controlled Release Society, 2015. BibTeX | Tags: @inproceedings{Caccavo:aa, title = {Hydrogels-based matrices behavior: experimental and modeling description}, author = {Diego Caccavo and Sara Cascone and Sabrina Bochicchio and Gaetano Lamberti and Annalisa Dalmoro and Anna Angela Barba}, year = {2015}, date = {2015-07-26}, booktitle = {42nd Annual Meeting & Exposition of the Controlled Release Society}, keywords = {}, pubstate = {published}, tppubtype = {inproceedings} } |
Caccavo, Diego; Apicella, Pietro; Cascone, Sara; Dalmoro, Annalisa; Lamberti, Gaetano; Barba, Anna Angela Hydrogels-based systems for controlled release in agricultural applications Inproceedings 42nd Annual Meeting & Exposition of the Controlled Release Society, 2015. BibTeX | Tags: Hydrogel Characterization @inproceedings{Caccavo2015b, title = {Hydrogels-based systems for controlled release in agricultural applications}, author = {Diego Caccavo and Pietro Apicella and Sara Cascone and Annalisa Dalmoro and Gaetano Lamberti and Anna Angela Barba }, year = {2015}, date = {2015-07-26}, booktitle = {42nd Annual Meeting & Exposition of the Controlled Release Society}, keywords = {Hydrogel Characterization}, pubstate = {published}, tppubtype = {inproceedings} } |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela Hydrogel-Based CRSs Analyses: Testing And Modeling Inproceedings 1st International Congress of Controlled Release Society - Greek Local Chapter, pp. 1–1, 1st International Congress of Controlled Release Society, Athens (Greece), 2015. BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @inproceedings{caccavo2015b, title = {Hydrogel-Based CRSs Analyses: Testing And Modeling}, author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba}, year = {2015}, date = {2015-05-01}, booktitle = {1st International Congress of Controlled Release Society - Greek Local Chapter}, pages = {1--1}, publisher = {1st International Congress of Controlled Release Society}, address = {Athens (Greece)}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {inproceedings} } |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela Controlled drug release from hydrogel-based matrices: Experiments and modeling. Journal Article International journal of pharmaceutics, 486 (1-2), pp. 144–152, 2015, ISSN: 1873-3476. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Modeling, Texture analysis, Transport phenomena, Water uptake @article{Caccavo2015a, title = {Controlled drug release from hydrogel-based matrices: Experiments and modeling.}, author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S0378517315002707}, doi = {10.1016/j.ijpharm.2015.03.054}, issn = {1873-3476}, year = {2015}, date = {2015-03-01}, journal = {International journal of pharmaceutics}, volume = {486}, number = {1-2}, pages = {144--152}, abstract = {Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches.}, keywords = {Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Modeling, Texture analysis, Transport phenomena, Water uptake}, pubstate = {published}, tppubtype = {article} } Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches. |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela Modeling the Drug Release from Hydrogel-Based Matrices Journal Article Molecular Pharmaceutics, 12 (2), pp. 474–483, 2015, ISSN: 1543-8384. Links | BibTeX | Tags: Hydrogel Modeling @article{Caccavo2015c, title = {Modeling the Drug Release from Hydrogel-Based Matrices}, author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba}, url = {http://pubs.acs.org/doi/abs/10.1021/mp500563n}, doi = {10.1021/mp500563n}, issn = {1543-8384}, year = {2015}, date = {2015-02-01}, journal = {Molecular Pharmaceutics}, volume = {12}, number = {2}, pages = {474--483}, publisher = {American Chemical Society}, chapter = {474}, keywords = {Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } |
Caccavo, Diego; Cascone, Sara; Amoroso, Maria Chiara; Apicella, Pietro; Lamberti, Gaetano; Barba, Anna Angela Hydrogel-based Granular Phytostrengtheners for Prolonged Release: Production and Characterization Journal Article Chemical Engineering Transaction, 44 , pp. 235–240, 2015. Abstract | Links | BibTeX | Tags: Granulation, Hydrogel Characterization, Tecnagri @article{Caccavo2015, title = {Hydrogel-based Granular Phytostrengtheners for Prolonged Release: Production and Characterization}, author = { Diego Caccavo and Sara Cascone and Maria Chiara Amoroso and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba}, url = {http://www.aidic.it/cet/15/44/040.pdf}, doi = {10.3303/CET1544040}, year = {2015}, date = {2015-01-01}, journal = {Chemical Engineering Transaction}, volume = {44}, pages = {235--240}, abstract = {Soil wellness is an indispensable requirement to obtain fruits and vegetables with finest quality and with high yields. To the purpose, periodical administrations of nutrients, as well as phytostrengtheners could be required. Crucial goals to maximize the economic and environmental sustainability of the whole cultivation are the decrease of the dosages number together with the increase of the active substance availability within the soil. With these aims a controlled release phytostrengtheners encapsulated in a granular Hydroxypropyl methylcellulose matrix has been developed exploiting the wet granulation process. The granular product has been analyzed in terms of Particle Size Distribution (PSD), morphology and flowability. The results showed the effectiveness of the granulation process and the good flowability of the granules, highly desirable features for the product handling and commercialization.}, keywords = {Granulation, Hydrogel Characterization, Tecnagri}, pubstate = {published}, tppubtype = {article} } Soil wellness is an indispensable requirement to obtain fruits and vegetables with finest quality and with high yields. To the purpose, periodical administrations of nutrients, as well as phytostrengtheners could be required. Crucial goals to maximize the economic and environmental sustainability of the whole cultivation are the decrease of the dosages number together with the increase of the active substance availability within the soil. With these aims a controlled release phytostrengtheners encapsulated in a granular Hydroxypropyl methylcellulose matrix has been developed exploiting the wet granulation process. The granular product has been analyzed in terms of Particle Size Distribution (PSD), morphology and flowability. The results showed the effectiveness of the granulation process and the good flowability of the granules, highly desirable features for the product handling and commercialization. |
Cascone, Sara; Apicella, Pietro; Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela Optimization of Chelates Production Process for Agricultural Administration of Inorganic Micronutrients Journal Article Chemical Engineering Transaction, 44 , pp. 217–222, 2015. Abstract | Links | BibTeX | Tags: Chelating Agents, Tecnagri @article{Cascone2015, title = {Optimization of Chelates Production Process for Agricultural Administration of Inorganic Micronutrients}, author = { Sara Cascone and Pietro Apicella and Diego Caccavo and Gaetano Lamberti and Anna Angela Barba}, url = {http://www.aidic.it/cet/15/44/037.pdf}, doi = {10.3303/CET1544037}, year = {2015}, date = {2015-01-01}, journal = {Chemical Engineering Transaction}, volume = {44}, pages = {217--222}, abstract = {The iron chlorosis is one of the most diffused plant disease, which affects their growth and reduces the yield of harvests. This disease is caused by the iron deficiency and it is highlighted by the progressive yellowing of plants due to the reduction of chlorophyll production. The most efficient and diffused therapy against the iron chlorosis is the use of chelating agents and, among them, the o,o-EDDHA/Fe3+, the most stable isomer of EDDHA, is the most used due to its capacity to guarantee a prolonged treatment. The aim of this work is to develop a production process environment friendly, based on the recovering and recycling of organic solvents to minimize the waste produced. The feed organic solvents ratio has been varied evaluating the synthesis yield and the percentage of o,o-EDDHA/Fe3+ produced to identify the best feeding conditions. Several products have been then tested on lettuce plants to determine their usability.}, keywords = {Chelating Agents, Tecnagri}, pubstate = {published}, tppubtype = {article} } The iron chlorosis is one of the most diffused plant disease, which affects their growth and reduces the yield of harvests. This disease is caused by the iron deficiency and it is highlighted by the progressive yellowing of plants due to the reduction of chlorophyll production. The most efficient and diffused therapy against the iron chlorosis is the use of chelating agents and, among them, the o,o-EDDHA/Fe3+, the most stable isomer of EDDHA, is the most used due to its capacity to guarantee a prolonged treatment. The aim of this work is to develop a production process environment friendly, based on the recovering and recycling of organic solvents to minimize the waste produced. The feed organic solvents ratio has been varied evaluating the synthesis yield and the percentage of o,o-EDDHA/Fe3+ produced to identify the best feeding conditions. Several products have been then tested on lettuce plants to determine their usability. |
2014 |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela Testing and modelling of hydrogels behavior for pharmaceutical and biomedical applications Inproceedings Proceedings of CHISA 2014, pp. 1–1, CHISA 2014, Prague, Czech Republic, 2014. BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @inproceedings{d.2014, title = {Testing and modelling of hydrogels behavior for pharmaceutical and biomedical applications}, author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba}, year = {2014}, date = {2014-08-01}, booktitle = {Proceedings of CHISA 2014}, pages = {1--1}, publisher = {CHISA 2014}, address = {Prague, Czech Republic}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {inproceedings} } |
Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Titomanlio, Giuseppe; Barba, Anna Angela In-vitro models of the gastro-intestinal tract for pharmaceutical and nutritional purposes Inproceedings Proceedings of CHISA 2014/PRES 2014, pp. 2–2, CHISA 2014, Prague, Czech Republic, 2014. BibTeX | Tags: In vitro, Pharmacokinetics @inproceedings{s.2014-4, title = {In-vitro models of the gastro-intestinal tract for pharmaceutical and nutritional purposes}, author = { Sara Cascone and Diego Caccavo and Gaetano Lamberti and Giuseppe Titomanlio and Anna Angela Barba}, year = {2014}, date = {2014-08-01}, booktitle = {Proceedings of CHISA 2014/PRES 2014}, pages = {2--2}, publisher = {CHISA 2014}, address = {Prague, Czech Republic}, keywords = {In vitro, Pharmacokinetics}, pubstate = {published}, tppubtype = {inproceedings} } |
Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela MODELING THE BEHAVIOR OF SWELLABLE HYDROGELS-BASED MATRICES FOR PHARMACEUTICAL APPLICATIONS Inproceedings 13th European Symposium on Controlled Drug Delivery, pp. 3–4, ESCDD 2014, Egmond aan Zee, The Netherlands, 2014. BibTeX | Tags: Hydrogel Modeling @inproceedings{s.2014, title = {MODELING THE BEHAVIOR OF SWELLABLE HYDROGELS-BASED MATRICES FOR PHARMACEUTICAL APPLICATIONS}, author = { Sara Cascone and Diego Caccavo and Gaetano Lamberti and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba}, year = {2014}, date = {2014-04-01}, booktitle = {13th European Symposium on Controlled Drug Delivery}, pages = {3--4}, publisher = {ESCDD 2014}, address = {Egmond aan Zee, The Netherlands}, keywords = {Hydrogel Modeling}, pubstate = {published}, tppubtype = {inproceedings} } |
2013 |
Schuster, Erich; Caccavo, Diego; Eckardt, Johanna; Altskär, Annika; Hermansson, Anne-Marie; Larsson, Anette; Ström, Anna Spontaneous formation of parallel aligned macropores within polysaccharide gels Inproceedings Materials for Tomorrow, 2013. Abstract | BibTeX | Tags: Alginate @inproceedings{Schuster2013, title = {Spontaneous formation of parallel aligned macropores within polysaccharide gels}, author = {Erich Schuster and Diego Caccavo and Johanna Eckardt and Annika Altsk\"{a}r and Anne-Marie Hermansson and Anette Larsson and Anna Str\"{o}m}, year = {2013}, date = {2013-10-02}, booktitle = {Materials for Tomorrow}, abstract = {The ability to control and direct mass transport of fluids and molecular components through soft biomaterials is of importance in a wide range of applications. Alginate is a biocompatible, renewable polymer source extracted from seaweed. The readily available anionic polysaccharide find commercial use in diverse areas such as wound care, pharmaceutics and food. Alginate forms a gel by rapid crosslinking with di- and tri-valent ions [1]. In this work we have used two different ways to introduce the multivalent ions that act as ion bridges between alginate. The methods are the "internal setting" [1] of the gels giving macroscopically homogeneous gels and “directed external” gelation [2] of the alginate giving rise to anisotropic growth of open capillaries running through the gel, see Figure 1. Our aim was to relate microstructural differences in the gels prepared by different methodologies to mass transport properties, and to determine the effect of various ions on the formation of channels. Although the same amount of calcium ions was present the porous calcium alginate gel had a local diffusion significantly higher compared to the corresponding gel without capillaries. The diameter and amount of capillaries could be tailored by using different types of ions from tenth to several hundreds of micrometers. By varying the preparation method and the type of ion for gelation we are able to form a biomaterial with different mass transport properties according to our needs. }, keywords = {Alginate}, pubstate = {published}, tppubtype = {inproceedings} } The ability to control and direct mass transport of fluids and molecular components through soft biomaterials is of importance in a wide range of applications. Alginate is a biocompatible, renewable polymer source extracted from seaweed. The readily available anionic polysaccharide find commercial use in diverse areas such as wound care, pharmaceutics and food. Alginate forms a gel by rapid crosslinking with di- and tri-valent ions [1]. In this work we have used two different ways to introduce the multivalent ions that act as ion bridges between alginate. The methods are the "internal setting" [1] of the gels giving macroscopically homogeneous gels and “directed external” gelation [2] of the alginate giving rise to anisotropic growth of open capillaries running through the gel, see Figure 1. Our aim was to relate microstructural differences in the gels prepared by different methodologies to mass transport properties, and to determine the effect of various ions on the formation of channels. Although the same amount of calcium ions was present the porous calcium alginate gel had a local diffusion significantly higher compared to the corresponding gel without capillaries. The diameter and amount of capillaries could be tailored by using different types of ions from tenth to several hundreds of micrometers. By varying the preparation method and the type of ion for gelation we are able to form a biomaterial with different mass transport properties according to our needs. |
Schuster, Erich; Caccavo, Diego; Eckardt, Johanna; Altskär, Annika; Hermansson, Anne-Marie; Larsson, Anette; Ström, Anna Microstructural, mechanical and mass transport properties of alginate capillary gels Inproceedings International Symposium on the Properties of Water, Fiskebäckskil, Sweden, 2013. @inproceedings{Schuster2013b, title = {Microstructural, mechanical and mass transport properties of alginate capillary gels}, author = {Erich Schuster and Diego Caccavo and Johanna Eckardt and Annika Altsk\"{a}r and Anne-Marie Hermansson and Anette Larsson and Anna Str\"{o}m}, year = {2013}, date = {2013-08-20}, booktitle = {International Symposium on the Properties of Water}, address = {Fiskeb\"{a}ckskil, Sweden}, keywords = {Alginate}, pubstate = {published}, tppubtype = {inproceedings} } |
2011 |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano Criteri per progettare e gestire il processo di granulazione Journal Article ICP Rivista dell'Industria Chimica, 4 , pp. 74–78, 2011. Abstract | BibTeX | Tags: Granulation @article{Caccavo2011, title = {Criteri per progettare e gestire il processo di granulazione}, author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti}, year = {2011}, date = {2011-01-01}, journal = {ICP Rivista dell'Industria Chimica}, volume = {4}, pages = {74--78}, abstract = {Un approccio ingegneristico, basato su poche misure e ripetibili, e coaudiuvato dalla modellazione fisico-matematica, pu\`{o} essere di grande aiuto nella gestione del processo di granulazione.}, keywords = {Granulation}, pubstate = {published}, tppubtype = {article} } Un approccio ingegneristico, basato su poche misure e ripetibili, e coaudiuvato dalla modellazione fisico-matematica, può essere di grande aiuto nella gestione del processo di granulazione. |