The publications of the members of the research group.
2020 |
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. |
Cascone, Sara; Lamberti, Gaetano Hydrogel-based commercial products for biomedical applications: a review Journal Article International Journal of Pharmaceutics, 573 (118803), pp. 1-19, 2020. Abstract | Links | BibTeX | Tags: biomedical applications, commercial products, drug delivery, Hydrogels @article{Cascone2019, title = {Hydrogel-based commercial products for biomedical applications: a review}, author = {Sara Cascone and Gaetano Lamberti}, url = {https://www.sciencedirect.com/science/article/pii/S0378517319308488?via%3Dihub}, doi = {10.1016/j.ijpharm.2019.118803}, year = {2020}, date = {2020-01-05}, journal = {International Journal of Pharmaceutics}, volume = {573}, number = {118803}, pages = {1-19}, abstract = {Hydrogels are hydrophilic polymer networks, able to absorb large amount of water, increasing their volume and showing a plethora of different material behaviors. Since their first practical application, dating from sixties of last century, they have been employed in several fields of biomedical sciences. After more than half a century of industrial uses, nowadays a lot of hydrogels are currently on the market for different purposes, and offering a wide spectra of features. In this review, even if it is virtually impossible to list all the commercial products based on hydrogels for biomedical applications, an extensive analysis of those materials that have reached the market has been carried out. The hydrogel-based materials used for drug delivery, wound dressing, tissue engineering, the building of contact lens, and hygiene products are enlisted and briefly described. A detailed snapshot of the set of these products that have reached the commercial maturity has been then obtained and presented. For each class of application, the basics of requirements are described, and then the materials are listed and classified on the basis of their chemical nature. For each product the commercial name, the producer, the chemical nature and the main characteristics are reported.}, keywords = {biomedical applications, commercial products, drug delivery, Hydrogels}, pubstate = {published}, tppubtype = {article} } Hydrogels are hydrophilic polymer networks, able to absorb large amount of water, increasing their volume and showing a plethora of different material behaviors. Since their first practical application, dating from sixties of last century, they have been employed in several fields of biomedical sciences. After more than half a century of industrial uses, nowadays a lot of hydrogels are currently on the market for different purposes, and offering a wide spectra of features. In this review, even if it is virtually impossible to list all the commercial products based on hydrogels for biomedical applications, an extensive analysis of those materials that have reached the market has been carried out. The hydrogel-based materials used for drug delivery, wound dressing, tissue engineering, the building of contact lens, and hygiene products are enlisted and briefly described. A detailed snapshot of the set of these products that have reached the commercial maturity has been then obtained and presented. For each class of application, the basics of requirements are described, and then the materials are listed and classified on the basis of their chemical nature. For each product the commercial name, the producer, the chemical nature and the main characteristics are reported. |
2017 |
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. |
2015 |
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. |
2014 |
Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis Journal Article Carbohydrate Polymers, 103 , pp. 348–354, 2014, ISSN: 01448617. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogels, Texture analysis, Water content @article{Cascone2014, title = {Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis}, author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S0144861713012757}, doi = {10.1016/j.carbpol.2013.12.060}, issn = {01448617}, year = {2014}, date = {2014-03-01}, journal = {Carbohydrate Polymers}, volume = {103}, pages = {348--354}, abstract = {The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force\textendashpenetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices.}, keywords = {Hydrogel Characterization, Hydrogels, Texture analysis, Water content}, pubstate = {published}, tppubtype = {article} } The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force–penetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices. |
2012 |
Dalmoro, Annalisa; Barba, Anna Angela; Lamberti, Gaetano; Grassi, Mario; D'Amore, Matteo Pharmaceutical applications of biocompatible polymer blends containing sodium alginate Journal Article Advances in Polymer Technology, 31 (3), pp. 219–230, 2012, ISSN: 07306679. Abstract | Links | BibTeX | Tags: Alginate gel film, Alginate shell{–}core particles, Biocompatibility, Crosslinking, Hydrogel Characterization, Hydrogels, Micro and Nano Vectors @article{Dalmoro2012a, title = {Pharmaceutical applications of biocompatible polymer blends containing sodium alginate}, author = { Annalisa Dalmoro and Anna Angela Barba and Gaetano Lamberti and Mario Grassi and Matteo D'Amore}, url = {http://doi.wiley.com/10.1002/adv.21276}, doi = {10.1002/adv.21276}, issn = {07306679}, year = {2012}, date = {2012-09-01}, journal = {Advances in Polymer Technology}, volume = {31}, number = {3}, pages = {219--230}, publisher = {Wiley Subscription Services, Inc., A Wiley Company}, abstract = {Biocompatible polymer blends, such as alginate blends, have a widespread use in pharmaceutical and medical applications due to their specific features, such as biodegradation, adhesiveness, and thermo- and pH sensitivity and that can be obtained from the mixture composition. In this work, the use of alginate blends was tested in a novel production methodology of therapeutic dosage forms based on polymeric chain reticulation phenomena induced by exposure to bivalent ions. Two kinds of sodium alginate were used to obtain gel films (structured films) in blends with Pluronic F127®. The blends were considered for applications in gel paving of drug-eluting stents. Sodium alginate was also used in shell\textendashcore particle production (structured particles) to obtain shell-barrier reducing drug release in the preparative steps (see wash operations). Both structures, films and particles, were obtained using Cu2+ and Ca2+ ions, respectively. Film/shell barrier properties were tested in dissolution experiments using vitamin B12 as an active molecule model. Experimental work demonstrated that the alginate composition is a crucial point in defining reticulated structures.}, keywords = {Alginate gel film, Alginate shell{\textendash}core particles, Biocompatibility, Crosslinking, Hydrogel Characterization, Hydrogels, Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } Biocompatible polymer blends, such as alginate blends, have a widespread use in pharmaceutical and medical applications due to their specific features, such as biodegradation, adhesiveness, and thermo- and pH sensitivity and that can be obtained from the mixture composition. In this work, the use of alginate blends was tested in a novel production methodology of therapeutic dosage forms based on polymeric chain reticulation phenomena induced by exposure to bivalent ions. Two kinds of sodium alginate were used to obtain gel films (structured films) in blends with Pluronic F127®. The blends were considered for applications in gel paving of drug-eluting stents. Sodium alginate was also used in shell–core particle production (structured particles) to obtain shell-barrier reducing drug release in the preparative steps (see wash operations). Both structures, films and particles, were obtained using Cu2+ and Ca2+ ions, respectively. Film/shell barrier properties were tested in dissolution experiments using vitamin B12 as an active molecule model. Experimental work demonstrated that the alginate composition is a crucial point in defining reticulated structures. |
Lamberti, Gaetano Parametric simulation of drug release from hydrogel-based matrices Journal Article Journal of Pharmacy and Pharmacology, 64 (1), pp. 48–51, 2012, ISSN: 00223573. Abstract | Links | BibTeX | Tags: drug release, FEM, HPMC, Hydrogels, modelling @article{Lamberti2012, title = {Parametric simulation of drug release from hydrogel-based matrices}, author = { Gaetano Lamberti}, url = {http://doi.wiley.com/10.1111/j.2042-7158.2011.01373.x}, doi = {10.1111/j.2042-7158.2011.01373.x}, issn = {00223573}, year = {2012}, date = {2012-01-01}, journal = {Journal of Pharmacy and Pharmacology}, volume = {64}, number = {1}, pages = {48--51}, publisher = {Blackwell Publishing Ltd}, abstract = {Objectives In this work a model recently proposed to describe the drug release from hydrogel-based matrices was applied to describe the fractional drug release from matrices based on hydroxypropylmethylcellulose (HPMC) and diclofenac. Methods The model, firstly proposed to describe the behaviour of systems based on HPMC and theophylline and a single set of preparation variables, is based on mass balances and transport phenomena evaluation and it was solved by an FEM-based numerical code. The experimental data on the HPMC\textendashdiclofenac matrices, taken from literature, have been obtained by varying the drug loading ratio, the compression force, the powder size of both the drug and the polymer. Key findings A good agreement between experimental data and model predictions, as calculated in the present work, was obtained without the use of any adjustable parameters. Conclusions The predictive nature of the model has been confirmed, even changing the drug molecule and other preparative parameters.}, keywords = {drug release, FEM, HPMC, Hydrogels, modelling}, pubstate = {published}, tppubtype = {article} } Objectives In this work a model recently proposed to describe the drug release from hydrogel-based matrices was applied to describe the fractional drug release from matrices based on hydroxypropylmethylcellulose (HPMC) and diclofenac. Methods The model, firstly proposed to describe the behaviour of systems based on HPMC and theophylline and a single set of preparation variables, is based on mass balances and transport phenomena evaluation and it was solved by an FEM-based numerical code. The experimental data on the HPMC–diclofenac matrices, taken from literature, have been obtained by varying the drug loading ratio, the compression force, the powder size of both the drug and the polymer. Key findings A good agreement between experimental data and model predictions, as calculated in the present work, was obtained without the use of any adjustable parameters. Conclusions The predictive nature of the model has been confirmed, even changing the drug molecule and other preparative parameters. |
2011 |
Lamberti, Gaetano; Galdi, Ivan; Barba, Anna Angela Controlled release from hydrogel-based solid matrices. A model accounting for water up-take, swelling and erosion. Journal Article International journal of pharmaceutics, 407 (1-2), pp. 78–86, 2011, ISSN: 1873-3476. Abstract | Links | BibTeX | Tags: drug release, Hydrogel Modeling, Hydrogels, Mathematical modeling, Swelling; Erosion @article{Lamberti2011, title = {Controlled release from hydrogel-based solid matrices. A model accounting for water up-take, swelling and erosion.}, author = { Gaetano Lamberti and Ivan Galdi and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S0378517311000548}, doi = {10.1016/j.ijpharm.2011.01.023}, issn = {1873-3476}, year = {2011}, date = {2011-04-01}, journal = {International journal of pharmaceutics}, volume = {407}, number = {1-2}, pages = {78--86}, abstract = {Design and realization of drug delivery systems based on polymer matrices could be greatly improved by modeling the phenomena which take place after the systems administration. Availability of a reliable mathematical model, able to predict the release kinetic from drug delivery systems, could actually replace the resource-consuming trial-and-error procedures usually followed in the manufacture of these latter. In this work, the complex problem of drug release from polymer (HPMC) based matrices systems was faced. The phenomena, previously observed and experimentally quantified, of water up-take, system swelling and erosion, and drug release were here described by transient mass balances with diffusion. The resulting set of differential equations was solved by using finite element methods. Two different systems were investigated: cylindrical matrices in which the transport phenomena were allowed only by lateral surfaces ("radial" case), and cylindrical matrices with the overall surface exposed to the solvent ("overall" case). A code able to describe quantitatively all the observed phenomena has been obtained.}, keywords = {drug release, Hydrogel Modeling, Hydrogels, Mathematical modeling, Swelling; Erosion}, pubstate = {published}, tppubtype = {article} } Design and realization of drug delivery systems based on polymer matrices could be greatly improved by modeling the phenomena which take place after the systems administration. Availability of a reliable mathematical model, able to predict the release kinetic from drug delivery systems, could actually replace the resource-consuming trial-and-error procedures usually followed in the manufacture of these latter. In this work, the complex problem of drug release from polymer (HPMC) based matrices systems was faced. The phenomena, previously observed and experimentally quantified, of water up-take, system swelling and erosion, and drug release were here described by transient mass balances with diffusion. The resulting set of differential equations was solved by using finite element methods. Two different systems were investigated: cylindrical matrices in which the transport phenomena were allowed only by lateral surfaces ("radial" case), and cylindrical matrices with the overall surface exposed to the solvent ("overall" case). A code able to describe quantitatively all the observed phenomena has been obtained. |