Publications

@article{nokey,

title = {Design of pH‑sensitive alginate\textendashcarbopol hydrogel patches for wound healing applications},

author = {Raffaella {De Piano} and Francesco Barra and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti},

url = {https://www.sciencedirect.com/science/article/pii/S0378517325013067?via%3Dihub},

doi = {10.1016/j.ijpharm.2025.126469},

year  = {2026},

date = {2026-01-20},

urldate = {2026-01-20},

journal = {International Journal of Pharmaceutics},

volume = {688},

abstract = {Smart wound dressings capable of responding to environmental stimuli of biological origin offer a promising strategy for infection management and accelerated healing. In this work, pH-sensitive hydrogel patches composed of alginate and Carbopol were developed for controlled release of a model antiseptic ingredient, the methylene blue agent. The systems were designed aiming to remain stable under acidic conditions (pH 5), favorable to wound healing, and to undergo swelling, erosion, and drug release under alkaline conditions (pH 8), which are typically associated with bacterial infection. Experimental characterization included swelling, erosion, and release studies under static (constant pH) and dynamically changing pH conditions. The realized composite patches showed minimal release at pH 5 and a rapid, complete release of methylene blue at pH 8, driven by pHinduced erosion. Then, a mathematical model was developed to describe the system’s behavior and successfully reproduced experimental data using a minimal set of adjustable parameters. The mathematical modeling approach adopted in this study was able to describe the experimental release kinetics with good accuracy when all kinetic rate constants were optimally fitted to the data confirming the erosion controlled release. These results highlight the potential of Carbopol\textendashalginate composites as effective pH-responsive wound dressings demonstrating controlled pH-triggered release behavior.},

keywords = {Hydrogel, Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Raft-forming systems in GERD therapies: Formulation guidelines},

author = {Raffaele Mancino and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti },

url = {https://www.sciencedirect.com/science/article/pii/S1773224725012110},

doi = {10.1016/j.jddst.2025.107808},

year  = {2026},

date = {2026-01-01},

journal = {Journal of Drug Delivery Science and Technology},

volume = {115},

abstract = {Gastroesophageal reflux disease (GERD) affects nearly 1 billion people globally and poses major health and economic challenges. While proton pump inhibitors (PPIs) are the mainstay of treatment, their long-term use raises safety concerns. Alginate-based raft-forming systems offer a non-systemic alternative, creating a floating gel barrier that prevents reflux by displacing the postprandial acid pocket. However, their efficacy varies with formulation, highlighting the need for a quantitative approach to design.

This study tested raft formulations combining two types of sodium alginates with varying amounts of sodium bicarbonate and calcium carbonate, using a factorial experimental design. Four key parameters were measured: raft strength, reflux resistance, pH buffering, and wet mass. Results showed that both alginate type and carbonate/bicarbonate ratios strongly affect raft performance.

Guidelines emerged: use alginates with strong gel-forming ability; optimize calcium carbonate (0.9\textendash1.0 mg/mg alginate) and sodium bicarbonate (0.4\textendash0.5 mg/mg); and maintain a balanced carbonate/bicarbonate ratio. Evaluating both mechanical and chemical properties is essential.

These findings support a rational, data-driven strategy for developing effective, personalized raft-forming therapies for GERD.},

keywords = {Hydrogel, Hydrogel Characterization},

pubstate = {published},

tppubtype = {article}

}

@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},

isbn = {218995},

year  = {2021},

date = {2021-06-16},

journal = {International Journal of Pharmaceutics},

volume = {605},

number = {120804},

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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@article{Dalmoro2016b,

title = { Injectable chitosan/b-glycerophosphate system for sustained release: gelation study, structural investigation and erosion tests},

author = {Annalisa Dalmoro and Michela Abrami and Barbara Galzerano and Sabrina Bochicchio and Anna Angela Barba and Mario Grassi and Domenico Larobina},

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/06.-Dalmoro-et-al-CDD-142-216-223-2017.pdf



http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/216/



},

doi = {10.2174/1567201813666160721142202},

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 = {216 - 223},

abstract = {Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turns, their possible uses in pharmacological and biomedical applications. In this study a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the “optimized composition”, namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release.},

keywords = {Hydrogel Characterization},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@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},

urldate = {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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@article{Lamberti2013a,

title = {Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis.},

author = { Gaetano Lamberti and Sara Cascone and Maria Margherita Cafaro and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba},

url = {http://www.sciencedirect.com/science/article/pii/S0144861712010193},

doi = {10.1016/j.carbpol.2012.10.003},

issn = {1879-1344},

year  = {2013},

date = {2013-01-01},

journal = {Carbohydrate polymers},

volume = {92},

number = {1},

pages = {765--8},

abstract = {In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms.},

keywords = {HPMC, Hydrogel Characterization, Texture analysis, Water content},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{Lamberti2012c,

title = {Controlled Release of Drugs From Hydrogel Based Matrices Systems: Experiments and Modeling},

author = { Gaetano Lamberti and Sara Cascone and Giuseppe Titomanlio and Anna Angela Barba},

issn = {0352-9568},

year  = {2012},

date = {2012-01-01},

journal = {Chemical and Biochemical Engineering Quarterly},

volume = {26},

number = {4},

pages = {321--330},

publisher = {Hrvatsko dru\v{s}tvo kemijskih in\v{z}enjera i tehnologa},

abstract = {Hydrogels are materials largely used in the formulation of pharmaceuticals since, in principle, they could produce a release system of zero-order kinetics, which is of great therapeutic interest. In this paper, a model was proposed for the description of the main transport phenomena involved in the drug release process from hydrogel matrices (water diffusion, polymer swelling, drug diffusion and polymer dissolution); the model predictions are successfully compared with a large set of experimental data, obtained working with matrices systems based on HPMC (Hydroxy Propyl Methyl Cellulose). The proposed model was found able to reproduce main features of the observed phenomena, it can thus be adopted for prediction of the performances of drug release systems from hydrogel matrices.},

keywords = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2009h,

title = {On the behavior of HPMC/Theophylline matrices for controlled drug delivery},

author = { Anna Angela Barba and Matteo D'Amore and Sara Cascone and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},

url = {http://doi.wiley.com/10.1002/jps.21701},

doi = {10.1002/jps.21701},

issn = {00223549},

year  = {2009},

date = {2009-11-01},

journal = {Journal of Pharmaceutical Sciences},

volume = {98},

number = {11},

pages = {4100--4110},

publisher = {Wiley Subscription Services, Inc., A Wiley Company},

abstract = {Design of systems for oral controlled release of drug could take advantages from the knowledge of which phenomena take place. In this work matrices obtained by powders compression (50:50, hydroxypropyl methylcellulose, a swelling hydrogel, and theophylline, a model drug) were immersed in water at 37 degrees C, allowing the water uptake and the drug release by lateral surface, confining the cylindrical matrices between glass slides. The tablets, after given immersion times, were withdrawn, cut in several annuli, and subsequently analyzed for the drug and the water concentration radial profiles. The data confirmed the pseudo-diffusive nature of the process, allowing to give a deep insight into the drug release process from swellable hydrogel matrices. In particular, it was confirmed the presence of nonhomogeneous gel layer, rich in water and poor in drug, with a profile of drug concentration which agrees well with a pseudo-diffusion phenomenon.},

keywords = {Diffusion, drug release, HPMC, Hydrogel Characterization, swellable hydrogels, Theophylline},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2009f,

title = {Swelling of cellulose derivative (HPMC) matrix systems for drug delivery},

author = { Anna Angela Barba and Matteo D'Amore and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},

url = {http://www.sciencedirect.com/science/article/pii/S0144861709002707},

doi = {10.1016/j.carbpol.2009.05.001},

issn = {01448617},

year  = {2009},

date = {2009-10-01},

journal = {Carbohydrate Polymers},

volume = {78},

number = {3},

pages = {469--474},

abstract = {The water swellable hydrogels are commonly used in the production of solid pharmaceutical dosage systems for oral administration (matrices). Their use allows to obtain the controlled drug release. The key role is played by the transport phenomena which take place: water up-take, gel swelling and erosion, increase in diffusivity due to hydration. Thus, knowledge of these phenomena is fundamental in designing and realizing the pharmaceutical systems. In this work, tablets made of pure hydrogel, HydroxyPropyl-MethylCellulose (HPMC), were produced and immersed in a thermostatic bath filled with stirred distilled water (37°C). The water up-take was allowed only by radial direction (from the lateral surface) by confining the tablet between two glass slides. Two distinct methods, an optical technique already described in a previous work, and a gravimetric procedure described here, were applied to measure the water concentration profiles along the radial direction in the tablets. The data obtained were used both to clarify the nature of the transport phenomena involved, and to perform a better tuning of a mathematical model previously proposed.},

keywords = {Erosion, Extended release, HPMC, Hydrogel Characterization, Swelling, Water diffusion},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2009e,

title = {Investigation of Pluronic© F127-Water solutions phase transitions by DSC and dielectric spectroscopy},

author = { Anna Angela Barba and Matteo D'Amore and Mario Grassi and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},

url = {http://doi.wiley.com/10.1002/app.30586},

doi = {10.1002/app.30586},

issn = {00218995},

year  = {2009},

date = {2009-10-01},

journal = {Journal of Applied Polymer Science},

volume = {114},

number = {2},

pages = {688--695},

publisher = {Wiley Subscription Services, Inc., A Wiley Company},

abstract = {The water solutions of the block copolymers PEOn-PPOm-PEOn, known as pluronics, show a complex thermal behavior, since they are liquid at low temperature (5°C), and they can give soft gel when heated at body temperature (37°C). These properties are of great interest in biomedical applications. To properly design these applications, a prerequisite is the knowledge of the thermodynamics\textemdashhow much\textemdashand of the kinetics\textemdashhow fast\textemdashwith which these transformations take place. In this work, solutions of F127 (the copolymer for which n = 100 and m = 65) were studied by varying the concentration and the temperature and analyzing their behavior when heated under several heating rates. The studies were performed by differential scanning calorimetry (DCS) and dielectric spectroscopy. The investigations carried out under equilibrium conditions allowed us to determine the thermodynamics of the phase transitions, whereas the investigations carried out under varying conditions allowed us to quantify the kinetics of the phase transitions. Empirical models were also proposed to describe both the thermodynamics and the kinetics observed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009},

keywords = {biological applications of polymers, block copolymers, dielectric properties, differential scanning calorimetry (DSC), gelation, Hydrogel Characterization},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2009a,

title = {Simultaneous measurement of theophylline and cellulose acetate phthalate in phosphate buffer by UV analysis},

author = { Anna Angela Barba and Serafina Chirico and Annalisa Dalmoro and Gaetano Lamberti},

year  = {2009},

date = {2009-01-01},

journal = {Can J Anal Sci Spectros},

volume = {53},

number = {6},

pages = {249--253},

abstract = {The oral administration of pH-sensitive drugs requires protecting the drug molecules from the acidic pH in the stomach: the simplest way is to use polymers as coating, especially polymers which are insoluble at low pH (in the stomach) and soluble under neutral conditions (in the intestine). The Cellulose Acetate Phosphate, CAP, is one of these polymers, and it is one of the most used coating polymers. Studies related to the behavior of such pharmaceutical systems require fast and accurate methods to assay the released drug concentration in dissolution medium. However, both the drug and the coating polymer are present in the dissolution bulk with unknown concentration, and they can interfere each other in assaying. In this communication, a simple method to assay, by UV analysis, Theophylline (TP) and Cellulose Acetate Phosphate concentrations in a dissolution medium, phosphate buffer pH 7.0 (BP), is proposed and validated.},

keywords = {Hydrogel Characterization},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2009b,

title = {Verso un rilascio intelligente},

author = { Anna Angela Barba and Gaetano Lamberti},

issn = {0393-3733},

year  = {2009},

date = {2009-01-01},

journal = {NCF-Notiziario Chimico Farmaceutico},

volume = {48},

number = {1},

pages = {68--71},

abstract = {L’efficacia di una terapia farmacologica dipende molto dal profi lo di rilascio del principio attivo dalla forma farmaceutica selezionata. In riferimento alla via di somministrazione orale, comprendere i fenomeni che si verificano dopo l’ingestione di una compressa \'{e} un passaggio fondamentale per poter ottimizzare le formulazioni e le tecniche di preparazione. Investigare tali fenomeni \'{e} uno degli scopi della nostra ricerca, e nell’articolo sono presentati e discussi alcuni risultati selezionati.},

keywords = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Chirico2007,

title = {Analysis and modeling of swelling and erosion behavior for pure HPMC tablet},

author = { Serafina Chirico and Annalisa Dalmoro and Gaetano Lamberti and Giuseppina Russo and Giuseppe Titomanlio},

url = {http://www.sciencedirect.com/science/article/pii/S0168365907003215},

doi = {10.1016/j.jconrel.2007.07.001},

issn = {01683659},

year  = {2007},

date = {2007-09-01},

journal = {Journal of Controlled Release},

volume = {122},

number = {2},

pages = {181--188},

abstract = {This work is focused on the transport phenomena which take place during immersion in water of pure hydroxypropylmethylcellulose tablets. The water uptake, the swelling and the erosion during immersion were investigated in drug-free systems, as a preliminary task before to undertake the study of drug-loaded ones. The tablets, obtained by powder compression, were confined between glass slabs to allow water uptake only by lateral surface and then immersed in distilled water at 37 °C, with simultaneous video-recording. By image analysis the normalized light intensity profiles were obtained and taken as a measure of the water mass fraction. The time evolutions of the total tablet mass, of the water mass and of the erosion radius were measured, too. Thus a novel method to measure polymer and water masses during hydration was pointed out. Then, a model consisting in the transient mass balance, accounting for water diffusion, diffusivity change due to hydration, swelling and erosion, was found able to reproduce all experimental data. Even if the model was already used in literature, the novelty of our approach is to compare model predictions with a complete set of experimental data, confirming that the main phenomena were correctly identified and described.},

keywords = {Controlled drug release, Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Swelling},

pubstate = {published},

tppubtype = {article}

}