The publications of the members of the research group.
2021
Sabrina Bochicchio; Gaetano Lamberti; Anna Angela Barba
Polymer–Lipid Pharmaceutical Nanocarriers: Innovations by New Formulations and Production Technologies Journal Article
In: Pharmaceutics, vol. 13(2), no. 198, pp. 15, 2021, ISSN: 19994923.
Abstract | Links | BibTeX | Tags: drug delivery, hybrid nanoparticles, lipids, nanotechnologies, polymers, production technologies
@article{Bochicchio2021,
title = {Polymer\textendashLipid Pharmaceutical Nanocarriers: Innovations by New Formulations and Production Technologies},
author = {Sabrina Bochicchio and Gaetano Lamberti and Anna Angela Barba},
editor = {Thomas Rades},
url = {https://www.mdpi.com/1999-4923/13/2/198/htm},
doi = {10.3390/pharmaceutics13020198},
issn = {19994923},
year = {2021},
date = {2021-02-02},
journal = {Pharmaceutics},
volume = {13(2)},
number = {198},
pages = {15},
abstract = {Some issues in pharmaceutical therapies such as instability, poor membrane permeability, and bioavailability of drugs can be solved by the design of suitable delivery systems based on the combination of two pillar classes of ingredients: polymers and lipids. At the same time, modern technologies are required to overcome production limitations (low productivity, high energy consumption, expensive setup, long process times) to pass at the industrial level. In this paper, a summary of applications of polymeric and lipid materials combined as nanostructures (hybrid nanocarriers) is reported. Then, recent techniques adopted in the production of hybrid nanoparticles are discussed, highlighting limitations still present that hold back the industrial implementation. },
keywords = {drug delivery, hybrid nanoparticles, lipids, nanotechnologies, polymers, production technologies},
pubstate = {published},
tppubtype = {article}
}
Some issues in pharmaceutical therapies such as instability, poor membrane permeability, and bioavailability of drugs can be solved by the design of suitable delivery systems based on the combination of two pillar classes of ingredients: polymers and lipids. At the same time, modern technologies are required to overcome production limitations (low productivity, high energy consumption, expensive setup, long process times) to pass at the industrial level. In this paper, a summary of applications of polymeric and lipid materials combined as nanostructures (hybrid nanocarriers) is reported. Then, recent techniques adopted in the production of hybrid nanoparticles are discussed, highlighting limitations still present that hold back the industrial implementation.
2020
Diego Caccavo; Gaetano Lamberti; Anna Angela Barba
Mechanics and drug release from poroviscoelastic hydrogels: Experiments and modeling Journal Article
In: European Journal of Pharmaceutics and Biopharmaceutics, vol. 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.
Sabrina Bochicchio; Annalisa Dalmoro; Gaetano Lamberti; Anna Angela Barba
Advances in Nanoliposomes Production for Ferrous Sulfate Delivery Journal Article
In: Pharmaceutics, vol. 12, no. 5, pp. 445, 2020.
Abstract | Links | BibTeX | Tags: drug delivery, ferrous sulfate, nanoliposome, simil-microfluidic apparatus, sonication
@article{Bochicchio2020b,
title = {Advances in Nanoliposomes Production for Ferrous Sulfate Delivery},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Gaetano Lamberti and Anna Angela Barba},
editor = {MDPI},
url = {https://www.mdpi.com/1999-4923/12/5/445/pdf},
doi = {10.3390/pharmaceutics12050445},
year = {2020},
date = {2020-05-11},
journal = {Pharmaceutics},
volume = {12},
number = {5},
pages = {445},
abstract = {In this study, a continuous bench scale apparatus based on microfluidic fluid dynamic principles was used in the production of ferrous sulfate-nanoliposomes for pharmaceutical/nutraceutical applications, optimizing their formulation with respect to the products already present on the market. After an evaluation of its fluid dynamic nature, the simil-microfluidic (SMF) apparatus was first used to study the effects of the adopted process parameters on vesicles dimensional features by using ultrasonic energy to enhance liposomes homogenization. Subsequently, iron-nanoliposomes were produced at different weight ratios of ferrous sulfate to the total formulation components (0.06, 0.035, 0.02, and 0.01 w/w) achieving, by using the 0.01 w/w, vesicles of about 80 nm, with an encapsulation efficiency higher than 97%, an optimal short- and long-term stability, and an excellent bioavailability in Caco-2 cell line. Moreover, a comparison realized between the SMF method and two more conventional production techniques showed that by using the SMF setup the process time was drastically reduced, and the process yield increased, achieving a massive nanoliposomes production. Finally, duty-cycle sonication was detected to be a scalable technique for vesicles homogenization. },
keywords = {drug delivery, ferrous sulfate, nanoliposome, simil-microfluidic apparatus, sonication},
pubstate = {published},
tppubtype = {article}
}
In this study, a continuous bench scale apparatus based on microfluidic fluid dynamic principles was used in the production of ferrous sulfate-nanoliposomes for pharmaceutical/nutraceutical applications, optimizing their formulation with respect to the products already present on the market. After an evaluation of its fluid dynamic nature, the simil-microfluidic (SMF) apparatus was first used to study the effects of the adopted process parameters on vesicles dimensional features by using ultrasonic energy to enhance liposomes homogenization. Subsequently, iron-nanoliposomes were produced at different weight ratios of ferrous sulfate to the total formulation components (0.06, 0.035, 0.02, and 0.01 w/w) achieving, by using the 0.01 w/w, vesicles of about 80 nm, with an encapsulation efficiency higher than 97%, an optimal short- and long-term stability, and an excellent bioavailability in Caco-2 cell line. Moreover, a comparison realized between the SMF method and two more conventional production techniques showed that by using the SMF setup the process time was drastically reduced, and the process yield increased, achieving a massive nanoliposomes production. Finally, duty-cycle sonication was detected to be a scalable technique for vesicles homogenization.
Anna Angela Barba; Annalisa Dalmoro; Sabrina Bochicchio; Veronica De Simone; Diego Caccavo; Marco Iannone; Gaetano Lamberti
Engineering approaches for drug delivery systems production and characterization Journal Article
In: 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},
urldate = {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.
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.
Sara Cascone; Gaetano Lamberti
Hydrogel-based commercial products for biomedical applications: a review Journal Article
In: International Journal of Pharmaceutics, vol. 573, no. 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.
2016
Annalisa Dalmoro; Anna Angela Barba; Gabriele Grassi; Mario Grassi; Gaetano Lamberti
In situ coronary stent paving by Pluronic F127–alginate gel blends: formulation and erosion tests Journal Article
In: Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 104, no. 5, pp. 1013-22, 2016.
Abstract | Links | BibTeX | Tags: coronary stent, drug delivery, erosion phenomena, gel erosion, pluronic/alginate blends
@article{Dalmoro2016b,
title = {In situ coronary stent paving by Pluronic F127\textendashalginate gel blends: formulation and erosion tests},
author = {Annalisa Dalmoro and Anna Angela Barba and Gabriele Grassi and Mario Grassi and Gaetano Lamberti},
url = {http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.33425/abstract;jsessionid=31C6676EE270B6362CB149075EE37B5F.f01t01},
doi = {10.1002/jbm.b.33425},
year = {2016},
date = {2016-07-01},
journal = {Journal of Biomedical Materials Research Part B: Applied Biomaterials},
volume = {104},
number = {5},
pages = {1013-22},
abstract = {In this work the development of an experimental protocol to perform the in situ gel-paving of coronary stent is presented. Biocompatible aqueous blends of Pluronic F127 and sodium alginates are used as potential drug dosage system for pharmacological in situ treatment of coronary in-stent restenosis. Pluronic F127/alginate aqueous blend has the unique characteristic to be liquid at room condition and to form gel at physiological temperature. The proposed protocol is based on the blend injection on stent wall previously implanted in a flexible silicon pipe mimicking the coronary artery. Injected blend is warmed up until human body temperature achieving a soft gel, then it is reticulated by copper bivalent ions to obtain an hard gel. To test the gel paving resistance to erosion phenomena when it is exposed to fluid flux (i.e. blood flux) a dedicated device, (the Simulated Artery Device, SAD), was built to simulate the human circulatory apparatus. The SAD is an hydraulic circuit in which a buffer solution (at pH 7.4) was fluxed by a peristaltic pump through the pipe hosting the covered stent. Erosion tests were performed monitoring, by gravimetric and spectrophotometric methods, the residual mass anchored to stent mesh after given times. The obtained results showed that the in situ gel-paving developed protocol was efficacious and reliable. The gel-paving was completely eroded in a time of the same order of magnitude of the physiological period required to restore the coronary lesion (subsequent to the atheroma removal) and of a pharmacological therapy to inhibit the in-stent-restenosis pathology. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.},
keywords = {coronary stent, drug delivery, erosion phenomena, gel erosion, pluronic/alginate blends},
pubstate = {published},
tppubtype = {article}
}
In this work the development of an experimental protocol to perform the in situ gel-paving of coronary stent is presented. Biocompatible aqueous blends of Pluronic F127 and sodium alginates are used as potential drug dosage system for pharmacological in situ treatment of coronary in-stent restenosis. Pluronic F127/alginate aqueous blend has the unique characteristic to be liquid at room condition and to form gel at physiological temperature. The proposed protocol is based on the blend injection on stent wall previously implanted in a flexible silicon pipe mimicking the coronary artery. Injected blend is warmed up until human body temperature achieving a soft gel, then it is reticulated by copper bivalent ions to obtain an hard gel. To test the gel paving resistance to erosion phenomena when it is exposed to fluid flux (i.e. blood flux) a dedicated device, (the Simulated Artery Device, SAD), was built to simulate the human circulatory apparatus. The SAD is an hydraulic circuit in which a buffer solution (at pH 7.4) was fluxed by a peristaltic pump through the pipe hosting the covered stent. Erosion tests were performed monitoring, by gravimetric and spectrophotometric methods, the residual mass anchored to stent mesh after given times. The obtained results showed that the in situ gel-paving developed protocol was efficacious and reliable. The gel-paving was completely eroded in a time of the same order of magnitude of the physiological period required to restore the coronary lesion (subsequent to the atheroma removal) and of a pharmacological therapy to inhibit the in-stent-restenosis pathology. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.
2015
Anna Angela Barba; Annalisa Dalmoro; Matteo D'Amore; Gaetano Lamberti
Liposoluble vitamin encapsulation in shell–core microparticles produced by ultrasonic atomization and microwave stabilization Journal Article
In: LWT - Food Science and Technology, vol. 64, no. 1, pp. 149–156, 2015, ISSN: 00236438.
Abstract | Links | BibTeX | Tags: drug delivery, Micro and Nano Vectors, Microwave drying, Shell{–}core microparticles, Ultrasonic energy, Vitamins
@article{Barba2015a,
title = {Liposoluble vitamin encapsulation in shell\textendashcore microparticles produced by ultrasonic atomization and microwave stabilization},
author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S002364381500403X},
doi = {10.1016/j.lwt.2015.05.040},
issn = {00236438},
year = {2015},
date = {2015-01-01},
journal = {LWT - Food Science and Technology},
volume = {64},
number = {1},
pages = {149--156},
abstract = {Encapsulation may protect unstable, fat soluble vitamins such as vitamin D2 (ergocalciferol). However, encapsulation by the solvent extraction and/or evaporation techniques can require toxic organic solvents, which greatly increase processing costs. The objective of this study was to evaluate the effect on ergocalciferol encapsulation by a combination of the ionic gelation method with the ultrasonic atomization and microwave drying. Optimization of manufacturing parameters included the addition of pluronic-F127 to the core solution at 1.5% w/w to increase the encapsulation efficiency to nearly 92%, greatly improving performance compared to Tween 80 at 0.5% w/w. Microwave treatment at 230 W promoted the recovery of 100% of the ergocalciferol and reduced drying times to about 30 min, while 690 W degraded 40% of the D2. In contrast, the conventional heating degraded 17% of the ergocalciferol during 12 h of processing. By all the applied methods, microparticles were produced with similar gastoresistance properties of less than 10% release at pH of 1.0, to nearly 100% release at pH of 6.8 and 240 min of dissolution. Analysis showed limited ergocalciferol degradation after 5 months of storage.},
keywords = {drug delivery, Micro and Nano Vectors, Microwave drying, Shell{\textendash}core microparticles, Ultrasonic energy, Vitamins},
pubstate = {published},
tppubtype = {article}
}
Encapsulation may protect unstable, fat soluble vitamins such as vitamin D2 (ergocalciferol). However, encapsulation by the solvent extraction and/or evaporation techniques can require toxic organic solvents, which greatly increase processing costs. The objective of this study was to evaluate the effect on ergocalciferol encapsulation by a combination of the ionic gelation method with the ultrasonic atomization and microwave drying. Optimization of manufacturing parameters included the addition of pluronic-F127 to the core solution at 1.5% w/w to increase the encapsulation efficiency to nearly 92%, greatly improving performance compared to Tween 80 at 0.5% w/w. Microwave treatment at 230 W promoted the recovery of 100% of the ergocalciferol and reduced drying times to about 30 min, while 690 W degraded 40% of the D2. In contrast, the conventional heating degraded 17% of the ergocalciferol during 12 h of processing. By all the applied methods, microparticles were produced with similar gastoresistance properties of less than 10% release at pH of 1.0, to nearly 100% release at pH of 6.8 and 240 min of dissolution. Analysis showed limited ergocalciferol degradation after 5 months of storage.
2011
Miguel Manzano; Gaetano Lamberti; Ivan Galdi; Marîa Vallet-Regî
Anti-Osteoporotic Drug Release from Ordered Mesoporous Bioceramics: Experiments and Modeling Journal Article
In: AAPS PharmSciTech, vol. 12, no. 4, pp. 1193–1199, 2011, ISSN: 1530-9932.
Abstract | Links | BibTeX | Tags: drug delivery, Modeling, ordered mesoporous matrices
@article{Manzano2011,
title = {Anti-Osteoporotic Drug Release from Ordered Mesoporous Bioceramics: Experiments and Modeling},
author = { Miguel Manzano and Gaetano Lamberti and Ivan Galdi and Mar\^{i}a Vallet-Reg\^{i}},
url = {http://www.springerlink.com/index/10.1208/s12249-011-9688-9},
doi = {10.1208/s12249-011-9688-9},
issn = {1530-9932},
year = {2011},
date = {2011-12-01},
journal = {AAPS PharmSciTech},
volume = {12},
number = {4},
pages = {1193--1199},
publisher = {Springer US},
abstract = {The release of a potent bone-resorption inhibitor such as zoledronate from a versatile drug delivery system such as SBA 15 has been modeled. The initial and boundary conditions have been defined, together with the system parameters, including the determination of equilibrium and transport parameters. Additionally, the experimental model of the same system has been observed to validate the prediction here developed. This approach represents a powerful tool for the designing of mesoporous implantable drug delivery systems because their release kinetics can be predicted in advance, and this leads to a considerable time and resources saving.},
keywords = {drug delivery, Modeling, ordered mesoporous matrices},
pubstate = {published},
tppubtype = {article}
}
The release of a potent bone-resorption inhibitor such as zoledronate from a versatile drug delivery system such as SBA 15 has been modeled. The initial and boundary conditions have been defined, together with the system parameters, including the determination of equilibrium and transport parameters. Additionally, the experimental model of the same system has been observed to validate the prediction here developed. This approach represents a powerful tool for the designing of mesoporous implantable drug delivery systems because their release kinetics can be predicted in advance, and this leads to a considerable time and resources saving.
2009
Anna Angela Barba; Annalisa Dalmoro; Felice De Santis; Gaetano Lamberti
Synthesis and characterization of P(MMA-AA) copolymers for targeted oral drug delivery Journal Article
In: Polymer Bulletin, vol. 62, no. 5, pp. 679–688, 2009, ISSN: 0170-0839.
Abstract | Links | BibTeX | Tags: drug delivery, Enteric coating, P(MMA-AA)
@article{Barba2009d,
title = {Synthesis and characterization of P(MMA-AA) copolymers for targeted oral drug delivery},
author = { Anna Angela Barba and Annalisa Dalmoro and Felice De Santis and Gaetano Lamberti},
url = {http://dx.doi.org/10.1007/s00289-009-0040-4},
doi = {10.1007/s00289-009-0040-4},
issn = {0170-0839},
year = {2009},
date = {2009-01-01},
journal = {Polymer Bulletin},
volume = {62},
number = {5},
pages = {679--688},
publisher = {Springer-Verlag},
abstract = {This paper describes the development of pH-sensitive poly(methyl methacrylate-acrylic acid) copolymers for the enteric coating of pharmaceutical products for oral administration. To obtain the dissolution at the desired pH level, different pH-sensitive polymers are available on the market. Usually, for each desired dissolution pH, an ad hoc polymer is designed. Thus, different dissolution pH values could ask for completely different polymers. Instead, the materials proposed in this work are copolymers of the same two monomers, and the different dissolution pH was obtained by changing the volume fraction of the hydrophobic methyl methacrylate monomer to the hydrophilic acrylic acid monomer. Increasing the volumetric percentage of methyl methacrylate causes the polymer to dissolve at increasing pH, until the dissolution does not take place at all, and it is replaced by a slow swelling phenomenon. The copolymers obtained were characterized by differential scanning calorimetry, in order to evaluate their glass transition temperature, and these latter were related to %MMA. The molecular weights of the pure polymers (PAA, PMMA) were measured by intrinsic viscosity, to further validate the glass transition temperatures observed. The dissolution of the copolymers was carefully tested in buffer solutions for a dense set of pH values. A linear relationship between dissolution pH and volumetric percentage of methyl methacrylate was obtained from these measurements. As a result, for any physiological compartment, the copolymer which dissolves at the pH of interest can be easily synthesized.},
keywords = {drug delivery, Enteric coating, P(MMA-AA)},
pubstate = {published},
tppubtype = {article}
}
This paper describes the development of pH-sensitive poly(methyl methacrylate-acrylic acid) copolymers for the enteric coating of pharmaceutical products for oral administration. To obtain the dissolution at the desired pH level, different pH-sensitive polymers are available on the market. Usually, for each desired dissolution pH, an ad hoc polymer is designed. Thus, different dissolution pH values could ask for completely different polymers. Instead, the materials proposed in this work are copolymers of the same two monomers, and the different dissolution pH was obtained by changing the volume fraction of the hydrophobic methyl methacrylate monomer to the hydrophilic acrylic acid monomer. Increasing the volumetric percentage of methyl methacrylate causes the polymer to dissolve at increasing pH, until the dissolution does not take place at all, and it is replaced by a slow swelling phenomenon. The copolymers obtained were characterized by differential scanning calorimetry, in order to evaluate their glass transition temperature, and these latter were related to %MMA. The molecular weights of the pure polymers (PAA, PMMA) were measured by intrinsic viscosity, to further validate the glass transition temperatures observed. The dissolution of the copolymers was carefully tested in buffer solutions for a dense set of pH values. A linear relationship between dissolution pH and volumetric percentage of methyl methacrylate was obtained from these measurements. As a result, for any physiological compartment, the copolymer which dissolves at the pH of interest can be easily synthesized.