@article{Piano}2024,

title = {Drug release from hydrogel-based matrix systems partially coated: experiments and modeling},

author = {Raffaella {De Piano} and Diego Caccavo and Sara Cascone and Caterina Festa and Gaetano Lamberti and Anna Angela Barba },

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092403044\&doi=10.1016%2fj.jddst.2020.102146\&partnerID=40\&md5=e519d84642480478a063b4c7b4e2832e},

doi = {10.1016/j.jddst.2020.102146},

isbn = {17732247},

year  = {2024},

date = {2024-05-01},

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

volume = {61},

number = {102146},

abstract = {Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics.},

keywords = {drug release, Modeling, Tablets, Theophylline},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2024,

title = {Analysis and simulation of wet-granulation processes},

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

url = {https://doi.org/10.1016/j.jtice.2024.105455},

year  = {2024},

date = {2024-03-22},

journal = {Journal of the Taiwan Institute of Chemical Engineers},

volume = {159},

number = {105455},

abstract = {Size enlargement by wet-granulation is one of the most important unit operation in several industrial fields: pharmaceutics, food processing, animal nutrition, agronomics, and so on. A lot of techniques have been used in order to measure the particle size distributions (PSD) and a few different approaches are available to model the PSD evolution during the process, mainly based on population balance equations (PBE). However, difficulties in both the activities (reliable measurement and robust modeling) have hindered their diffusion in industrial practice, keeping the granulation closer to an art than to a science.},

keywords = {Dynamic image analysis, Modeling, Particle size distribution, Population balance equation, Wet-granulation},

pubstate = {published},

tppubtype = {article}

}

@article{Mancino2023,

title = {Agarose Cryogels: Production Process Modeling and Structural Characterization },

author = {Raffaele Mancino and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti and Alice Biasin and Angelo Cortesi and Gabriele Grassi and Mario Grassi and Michela Abrami},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85172281028\&doi=10.3390%2fgels9090765\&partnerID=40\&md5=7753d30977c1b97694c4ede138749d57},

doi = {10.3390/gels9090765},

issn = {23102861},

year  = {2023},

date = {2023-09-20},

journal = {Gels},

volume = {9},

number = {9},

pages = {765},

abstract = {A cryogel is a cross-linked polymer network with different properties that are determined by its manufacturing technique. The formation of a cryogel occurs at low temperatures and results in a porous structure whose pore size is affected by thermal conditions. The adjustable pore sizes of cryogels make them attractive for diverse applications. In this study, the influence of the external operational temperature, which affects the cooling and freezing rates, on the production of cryogels with 2% w/w agarose is investigated. Moreover, a mathematical model is developed to simulate the cryogel production process and provide an initial estimate of the pore size within the structure. The predictions of the model, supported by qualitative light microscopy images, demonstrate that cryogels produced at higher process temperatures exhibit larger pore sizes. Moreover, the existence of pore size distribution within the gel structure is confirmed. Finally, stress relaxation tests, coupled with an image analysis, validates that cryogels produced at lower temperatures possess a higher stiffness and slower water release rates.},

keywords = {Agarose, cryogels, Equilibrium, Hydrogels, Modeling, Rheology},

pubstate = {published},

tppubtype = {article}

}

@article{Piano}2023b,

title = {Polyelectrolyte hydrogels in biological systems: Modeling of swelling and deswelling behavior},

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

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85161532217\&doi=10.1016%2fj.ces.2023.118959\&partnerID=40\&md5=a269515dd96617e9242f75711516e847},

doi = {10.1016/j.ces.2023.118959},

issn = {00092509},

year  = {2023},

date = {2023-09-05},

journal = {Chemical Engineering Science},

volume = {279},

number = {118959},

abstract = {Polyelectrolyte hydrogels are a particular class of hydrogel whose behavior is connected to the variation of pH in the surrounding solution. Their behavior is influenced by the ionizable groups present on their chain. These groups could be acid or basic and polyelectrolytes could be anionic or cationic. To fully understand their behavior mathematical modeling has been widely used over many years. In this work a model based on a monophasic approach will be used to describe a general behavior of anionic hydrogels in a steady state condition at pH lower (or equal) to seven. Free swelling experiments and constrained swelling experiments have been simulated varying the parameters of the model to highlight the properties of the material. From a comparison with experimental data, it results that the proposed model can describe the general behavior of the system as described in the literature.},

keywords = {Biological systems, Equilibrium, Hydrogels, Modeling, Polyelectrolytes},

pubstate = {published},

tppubtype = {article}

}

@article{Piano}2020,

title = {Drug release from hydrogel-based matrix systems partially coated: experiments and modeling},

author = {Raffaella {De Piano} and Diego Caccavo and Sara Cascone and Caterina Festa and Gaetano Lamberti and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/abs/pii/S1773224720314350?via%3Dihub},

doi = {10.1016/j.jddst.2020.102146},

year  = {2020},

date = {2020-10-07},

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

abstract = {Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics.},

keywords = {drug release, Modeling, Tablets, Theophylline},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{Barba2020,

title = {Engineering approaches for drug delivery systems production and characterization},

author = {Anna Angela Barba and Annalisa Dalmoro and Sabrina Bochicchio and Veronica De Simone and Diego Caccavo and Marco Iannone and Gaetano Lamberti},

url = {https://www.sciencedirect.com/science/article/pii/S0378517320302519},

doi = {10.1016/j.ijpharm.2020.119267},

year  = {2020},

date = {2020-03-31},

journal = {International Journal of Pharmaceutics},

abstract = {To find and to test the therapeutic effectiveness (and the limited adverse effects) of a new drug is a long and expensive process. It has been estimated a period of ten years and an expense of the order of one billion USD are required. Meanwhile, even if a promising molecule has been identified, there is the need for operative methods for its delivery. The extreme case is given by gene therapy, in which molecules with tremendous in-vitro efficacy cannot be used in practice because of the lack in useful vector systems to deliver them. Most of the recent efforts in pharmaceutical sciences are focused on the development of novel drug delivery systems (DDSs).

In this review, the work done recently on the development and testing of novel DDSs, with particular emphasis on the results obtained by European research, is summarized. In the first section of the review the DDSs are analyzed accordingly with their scale-size: starting from nano-scale (liposomes, nanoparticles), up to the micro-scale (microparticles), until the macroscopic world is reached (granules, matrix systems). In the following two sections, non-conventional testing methods (mechanical methods and bio-relevant dissolution methods) are presented; at last, the importance of mathematical modeling to describe drug release and related phenomena is reported.},

keywords = {drug delivery, Hydrogel, Innovation in Europe, Microvectors, Modeling, Nanovectors},

pubstate = {published},

tppubtype = {article}

}

@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{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},

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{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}

}