Sara Cascone

@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{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{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}

}

@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{Cascone2018,

title = {A physiologically-based model to predict individual pharmacokinetics and pharmacodynamics of remifentanil},

author = {Sara Cascone and Gaetano Lamberti and Ornella Piazza and Roberto Andrea Abbiati and Davide Manca},

url = {http://www.sciencedirect.com/science/article/pii/S0928098717305201},

doi = {10.1016/j.ejps.2017.09.028},

issn = {0928-0987},

year  = {2018},

date = {2018-01-01},

journal = {European Journal of Pharmaceutical Sciences},

volume = {111},

pages = {20-28},

abstract = {Remifentanil based anesthesia is nowadays spread worldwide. This drug is characterized by a rapid onset of the analgesic effects, but also by a rapid onset of the side effects. For this reason, the knowledge of the remifentanil concentration in the human body is a key topic in anesthesiology. The aims of this work are to propose and validate a physiologically based pharmacokinetic model capable to predict both the pharmacokinetics and pharmacodynamics of remifentanil, and to take into account the inter-individual differences among the patients (such as height and body mass). The blood concentration of remifentanil has been successfully simulated and compared with experimental literature data. The pharmacodynamics, in terms of effect of remifentanil on minute ventilation and electroencephalogram, has been implemented in this model. Moreover, the remifentanil concentration in various organs and tissues is predicted, which is a significant improvement with respect to the traditional compartmental models. The availability of the model makes possible the prediction of the effects of remifentanil administration, also accounting for individual parameters.},

keywords = {Modeling, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2017b,

title = {HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture},

author = {Diego Caccavo and Sara Cascone and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba},

url = {http://www.tandfonline.com/doi/full/10.1080/00986445.2017.1362398},

doi = {10.1080/00986445.2017.1362398 },

issn = {0098-6445},

year  = {2017},

date = {2017-12-01},

journal = {Chemical Engineering Communications},

volume = {204},

number = {12},

pages = {1333-1340},

abstract = {One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.},

keywords = {Granulation, HPMC},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2017b,

title = {Mimicking the contractions of a human stomach and their effect on pharmaceuticals},

author = {Sara Cascone and Felice {De Santis} and Gaetano Lamberti},

url = {http://www.sciencedirect.com/science/article/pii/S1773224717305907},

doi = {10.1016/j.jddst.2017.09.008},

issn = {1773-2247},

year  = {2017},

date = {2017-10-01},

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

volume = {41},

pages = {454-461},

abstract = {The prediction of the drug’s fate, once it is released from a pharmaceutical form, is one of the key topic in pharmaceutics and, to evaluate its release kinetics and effectiveness, the reproduction of the mixing conditions experienced by the pharmaceutical system is necessary. In this work a device reproducing the peristaltic waves of the stomach is presented, in order to obtain more reliable drug release profiles. Extended release commercial tablets of diclofenac were tested using both the conventional dissolution method and the new in vitro model proposed. The release profiles obtained using the conventional method and using the artificial stomach were found different both in shape and in magnitude. In particular, a drug concentration gradient along the stomach was realized, reflecting the poor mixing behavior in the model, similarly to what happen in the real physiology. Furthermore, also during the second stage of dissolution the evolutions were different, probably due to the higher shear experienced by the tablet during the first stage in the novel apparatus. The plasma concentration evolutions were predicted by a pharmacokinetic model starting from in vitro dissolution profiles. The comparison of the plasma concentrations confirmed that the dissolution kinetics strongly influences the drug evolution in the human body.},

keywords = {Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2017,

title = {Modeling and comparison of release profiles: Effect of the dissolution method},

author = {Sara Cascone},

url = {http://www.sciencedirect.com/science/article/pii/S092809871730355X},

doi = {10.1016/j.ejps.2017.06.021},

issn = {0928-0987},

year  = {2017},

date = {2017-08-30},

journal = {European Journal of Pharmaceutical Sciences},

volume = {106},

pages = {352-361},

abstract = {During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach.

Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified.},

keywords = {drug release, In silico, In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{NPC01,

title = {Encapsulation of Active Molecules in Microparticles Based on Natural Polysaccharides},

author = {Annalisa Dalmoro and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},

url = {http://www.naturalproduct.us/index.asp

https://www.gruppotpp.it/wp-content/uploads/2017/06/Dalmoro-et-al-NPC-126-863-866-2017-Abstract-1.pdf},

issn = {1934-578X},

year  = {2017},

date = {2017-07-31},

journal = {Natural Product Communications},

volume = {12},

number = {6},

pages = {863-866},

abstract = {This mini-review is focused on an engineering approach to produce polysaccharides-based microparticles for nutraceutical and pharmaceutical purposes. A brief introduction about the fundamental properties of polysaccharides and their use as microsystems in food, cosmetics, and pharmaceutics, and a summary of the most important methods of preparation are described. Then, a novel method based on the ultrasonic atomization of solutions of the two most used polysaccharides, alginate and chitosan, followed by ionotropic gelation to produce enteric microsystems for oral administration and, in particular, the basic mechanisms of the encapsulation of molecules with different size and hydrophilicity, are investigated. This mini-review will show therefore the pathway to correctly design a polysaccharide microcarrier for the encapsulation of active molecules with different properties: from the choice of materials features, to the selection and the optimization of production methods with the aim to reduce costs and energy (ionotropic gelation coupled to ultrasonic atomization), to the control of the final carrier size (by purposely developed predictive models), at last to the optimization of encapsulation properties (predicting by model the drug leakage and providing different solutions to avoid it).},

keywords = {Micro and Nano Vectors, microencapsulation, ultrasonic atomization},

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{Barba2017,

title = {Engineering approaches in siRNA delivery},

author = {Anna Angela Barba and Sara Cascone and Diego Caccavo and Gaetano Lamberti and Gianluca Chiarappa and Michela Abrami and Gabriele Grassi and Mario Grassi and Giovanna Tomaiuolo and Stefano Guido and Valerio Brucato and Francesco {Carf\`{i} Pavia} and Giulio Ghersi and Vincenzo {La Carrubba} and Roberto Andrea Abbiati and Davide Manca},

url = {http://www.sciencedirect.com/science/article/pii/S0378517317301138},

doi = {10.1016/j.ijpharm.2017.02.032},

year  = {2017},

date = {2017-06-20},

journal = {International Journal of Pharmaceutics},

volume = {525},

number = {2},

pages = {343\textendash358},

abstract = {siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors’ production processes and siRNAs vectors’ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors’ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2017,

title = {Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method},

author = {Annalisa Dalmoro and Alexander Y. Sitenkov and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},

url = {http://www.sciencedirect.com/science/article/pii/S037851731631198X},

doi = {10.1016/j.ijpharm.2016.12.056},

year  = {2017},

date = {2017-02-25},

journal = {International Journal of Pharmaceutics},

volume = {518},

number = {1-2},

pages = {50\textendash58},

abstract = {In this study a protocol exploiting the combination of the ultrasonic atomization and the complexation between polyelectrolytes was developed to efficiently encapsulate a hydrophilic chemotherapeutic agent essentially used in the treatment of colon cancer, 5-fluorouracil, in enteric shell-core alginate-based microcarriers. The atomization assisted by ultrasound allowed to obtain small droplets by supplying low energy and avoiding drug degradation. In particular microcarriers were produced in a home-made apparatus where both the core (composed of alginate, drug, and Pluronic F127) and shell (composed of only alginate) feed were separately sent to the coaxial ultrasonic atomizer where they were nebulized and placed in contact with the complexation bulk. With the aim to obtain microstructured particles of alginate encapsulating 5-fluorouracil, different formulations of the first complexation bulk were tested; at last an emulsion made of a calcium chloride aqueous solution and dichloromethane allowed to reach an encapsulation efficiency of about 50%. This result can be considered very interesting considering that in literature similar techniques gave 5-fluorouracil encapsulation efficiencies of about 10%.



Since a single complexation stage was not able to assure microcarriers gastroresistance, the formulation of a second complexation bulk was evaluated. The solution of cationic and pH-insoluble Eudragit® RS 100 in dichloromethane was chosen as bulk of second-stage complexation obtaining good enteric properties of shell-core microcarriers, i.e. a 5-FU cumulative release at pH 1 (simulating gastric pH) lower than 35%. The formation of interpolyelectrolyte complex (IPEC) between countercharged polymers and the chemical stability of 5-FU in microcarriers were confirmed by FTIR analysis, the presence of an amorphous dispersion of 5-FU in prepared microparticles was also confirmed by DSC. Finally, shell-core enteric coated microcarriers encapsulating 5-fluorouracil were used to prepare tablets, which can be potentially used as oral administration dosage systems for their 5-fluorouracil slower release.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Chiarappa2016,

title = {Chemical Engineering in the “BIO” world},

author = {Gianluca Chiarappa and Mario Grassi and Michela Abrami and Roberto Andrea Abbiati and Anna Angela Barba and Anja Boisen and Valerio Brucato and Giulio Ghersi and Diego Caccavo and Sara Cascone and Sergio Caserta and Nicola Elvassore and Monica Giomo and Stefano Guido and Gaetano Lamberti and Domenico Larobina and Davide Manca and Paolo Marizza and Giovanna Tomaiuolo and Gabriele Grassi },

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/02.-Chiarappa-et-al-CDD-142-158-178-2017.pdf

http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/158/},

doi = {10.2174/1567201813666160602230550},

year  = {2017},

date = {2017-02-08},

issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},

journal = {Current Drug Delivery},

volume = {14},

number = {2},

pages = {158 - 178},

abstract = {Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2016b,

title = {Drug delivery from hydrogels: a general framework for the release modeling},

author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson },

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/03.-Caccavo-et-al-CDD-142-179-189-2017.pdf

http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/179/},

doi = {10.2174/1567201813666160808102106},

year  = {2017},

date = {2017-02-08},

issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},

journal = {Current Drug Delivery},

volume = {14},

number = {2},

pages = {179 - 189},

abstract = {The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components.},

keywords = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2016,

title = {Gastrointestinal behavior and ADME phenomena: I. In vitro simulation},

author = {Sara Cascone and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio and Matteo d'Amore and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/pii/S1773224716302659

},

doi = {10.1016/j.jddst.2016.08.002},

issn = {1773-2247},

year  = {2016},

date = {2016-10-01},

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

volume = {35},

pages = {272-283},

abstract = {The most common administration route for pharmaceuticals is the oral one. A drug orally administered has to undergo several processes in order to carry out its therapeutic potential. The pharmaceutical has to dissolve and to release the API (Active Pharmaceutical Ingredient) in the desired location along the GI (Gastro Intestinal) tract, to pass through the intestinal wall, to overcome the liver (first-pass metabolism), and finally to reach the plasma, where it has to be stable during its travel toward the target organ/tissue. The key roles in this complex framework are played by the design (such as matrices, reservoirs, enteric systems) and the testing of the pharmaceuticals.



This review is focused on the state of the art in the pharmaceutical testing methods, carried out by the simulation of what happens once the pharmaceutical has been administered, investigating the in vitro approach. In the first section, the generalities of the dissolution and the ADME (Adsorption, Distribution, Metabolism and Excretion) phenomena are investigated. In the second section, the in vitro apparatuses are described, with a special focus on the role of food in their design and behavior. Some case histories of application for each approach are also discussed.},

keywords = {Biodistribution, In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Piazza2016b,

title = {The effect of liver esterases and temperature on remifentanil degradation in vitro},

author = {Ornella Piazza and Sara Cascone and Linda Sessa and Edoardo {De Robertis} and Gaetano Lamberti},

url = {http://www.sciencedirect.com/science/article/pii/S0378517316305191},

doi = {10.1016/j.ijpharm.2016.06.043},

year  = {2016},

date = {2016-07-04},

journal = {International Journal of Pharmaceutics},

volume = {510},

number = {1},

pages = {359\textendash364},

abstract = {Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients.The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed.Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.},

keywords = {In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Lamberti2016,

title = {Gastrointestinal behavior and ADME phenomena: II. in silico simulation},

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

url = {http://www.sciencedirect.com/science/article/pii/S1773224716302118},

doi = {10.1016/j.jddst.2016.06.014},

issn = {1773-2247},

year  = {2016},

date = {2016-07-04},

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

volume = {35},

pages = {165-171},

abstract = {The main goal of the pharmacokinetic modeling is the prediction of the drug concentration in the blood, tissues, and organs. The approaches to the modeling of physiological phenomena can be different on the basis of the details used to describe the Adsorption, Distribution, Metabolism, and Excretion (ADME) phenomena.



This review is focused on the state of the art in the pharmacokinetic modeling, on the different approaches used to describe the drug fate once it is administered. In particular, the early and the recent developments in the pharmacokinetic and in the gastrointestinal behavior modeling are discussed, together with some case histories of their applications.},

keywords = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Apicella2016,

title = {Iron Chelates: Production Processes and Reaction Evolution Analysis},

author = {Pietro Apicella and Sara Cascone and Felice De Santis and Gaetano Lamberti },

url = {http://www.tandfonline.com/doi/abs/10.1080/00986445.2015.1114476?journalCode=gcec20},

doi = {10.1080/00986445.2015.1114476},

year  = {2016},

date = {2016-01-16},

journal = {Chemical Engineering Communications},

abstract = {Nowadays, fertilization using synthetic chelates is the most common technique to solve the iron chlorosis, a disease which affects the plants growth. The ethylenediamine-N,N’-bis(o-hydroxyphenyl) acetic acid (EDDHA) is among the most efficient iron chelating agents. To produce EDDHA, a reaction has been performed using as reactants: phenol, ethylenediamine, glyoxylic acid, and sodium hydroxide. To study the reaction kinetics, samples have been withdrawn from the reactor during the reaction and the kinetics has been quantified, evaluating the yield evolution during the reaction phase. This study has been useful to optimize the reaction time. Then, a catalyst has been added to the reaction mixture, to analyze its effect on the reaction evolution. Comparing the reaction evolution of the non-catalyzed and the catalyzed reaction protocols, two main results have to be highlighted: the time to reach the final yield is lower than the one proposed in literature and the used catalyst has a minimum effect on the reaction rate.},

keywords = {Chelating Agents},

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}

}

@article{Caccavo2015c,

title = {Modeling the Drug Release from Hydrogel-Based Matrices},

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

url = {http://pubs.acs.org/doi/abs/10.1021/mp500563n},

doi = {10.1021/mp500563n},

issn = {1543-8384},

year  = {2015},

date = {2015-02-01},

journal = {Molecular Pharmaceutics},

volume = {12},

number = {2},

pages = {474--483},

publisher = {American Chemical Society},

chapter = {474},

keywords = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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{Cascone2015,

title = {Optimization of Chelates Production Process for Agricultural Administration of Inorganic Micronutrients},

author = { Sara Cascone and Pietro Apicella and Diego Caccavo and Gaetano Lamberti and Anna Angela Barba},

url = {http://www.aidic.it/cet/15/44/037.pdf},

doi = {10.3303/CET1544037},

year  = {2015},

date = {2015-01-01},

journal = {Chemical Engineering Transaction},

volume = {44},

pages = {217--222},

abstract = {The iron chlorosis is one of the most diffused plant disease, which affects their growth and reduces the yield of harvests. This disease is caused by the iron deficiency and it is highlighted by the progressive yellowing of plants due to the reduction of chlorophyll production. The most efficient and diffused therapy against the iron chlorosis is the use of chelating agents and, among them, the o,o-EDDHA/Fe3+, the most stable isomer of EDDHA, is the most used due to its capacity to guarantee a prolonged treatment. The aim of this work is to develop a production process environment friendly, based on the recovering and recycling of organic solvents to minimize the waste produced. The feed organic solvents ratio has been varied evaluating the synthesis yield and the percentage of o,o-EDDHA/Fe3+ produced to identify the best feeding conditions. Several products have been then tested on lettuce plants to determine their usability.},

keywords = {Chelating Agents, Tecnagri},

pubstate = {published},

tppubtype = {article}

}

@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{Cascone2013,

title = {Pharmacokinetics of Remifentanil: a three-compartmental modeling approach},

author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Ornella Piazza},

url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829787/},

issn = {2239-9747},

year  = {2013},

date = {2013-09-01},

journal = {Translational Medicine @ UniSa},

volume = {7},

pages = {18--22},

publisher = {Universit},

abstract = {Remifentanil is a new opioid derivative drug characterized by a fast onset and by a short time of action, since it is rapidly degraded by esterases in blood and other tissues. Its pharmacokinetic and pharmacodynamics properties make remifentanil a very interesting molecule in the field of 0anesthesia. However a complete and versatile pharmacokinetic description of remifentanil still lacks. In this work a three-compartmental model has been developed to describe the pharmacokinetics of remifentanil both in the case in which it is administered by intravenous constant-rate infusion and by bolus injection. The model curves have been compared with experimental data published in scientific papers and the model parameters have been optimized to describe both ways of administration. The ad hoc model is adaptable and potentially useful for predictive purposes.},

keywords = {In silico, Pharmacokinetics},

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{Cascone2012,

title = {Microencapsulation effectiveness of small active molecules in biopolymer by ultrasonic atomization technique},

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

url = {http://www.tandfonline.com/doi/full/10.3109/03639045.2011.653814},

doi = {10.3109/03639045.2011.653814},

issn = {0363-9045},

year  = {2012},

date = {2012-12-01},

journal = {Drug Development and Industrial Pharmacy},

volume = {38},

number = {12},

pages = {1486--1493},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Lamberti2012d,

title = {In vitro simulation of drug intestinal absorption.},

author = { Gaetano Lamberti and Sara Cascone and Margherita Iannaccone and Giuseppe Titomanlio},

url = {http://www.sciencedirect.com/science/article/pii/S0378517312009520},

doi = {10.1016/j.ijpharm.2012.10.012},

issn = {1873-3476},

year  = {2012},

date = {2012-12-01},

journal = {International journal of pharmaceutics},

volume = {439},

number = {1-2},

pages = {165--8},

abstract = {In this work, a simple set-up was designed, realized and tested to evaluate the effect of intestinal absorption on the in vitro drug release studies. The conventional USP-approved dissolution apparatus 2 was equipped with an hollow fibers filter, along with the necessary tubing and pumps, to simulate the two-fluids real behavior (the gastro intestinal lumen and the gastro intestinal circulatory system). The realized set-up was characterized in term of mass exchange characteristic, using the theophylline as the model drug, also with the aid of a simple mathematical model; then the release kinetics of a controlled release tablet was evaluated in the conventional test as well as in the novel simulator. The concentration of drug in the release compartment (which simulates the gastric lumen) was found lower in the novel simulator than in the traditional one.},

keywords = {Controlled drug release, In vitro, Intestinal Absorption, Mass balance, Oral administration, Pharmacokinetics, Theophylline},

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{Lamberti2012b,

title = {An engineering approach to biomedical sciences: advanced testing methods and pharmacokinetic modeling},

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

year  = {2012},

date = {2012-01-01},

journal = {Translational Medicine@ UniSa},

volume = {4},

pages = {34--38},

publisher = {Universit},

abstract = {In this paper, the philosophy of a research in pharmacology field, driven by an engineering approach, was described along with some case histories and examples. The improvement in the testing methods for pharmaceutical systems (in-vitro techniques), as well as the proposal and the testing of mathematical models to describe the pharmacokinetics (in-silico techniques) are reported with the aim of pointing out methodologies and tools able to reduce the need of expensive and ethical problematic in-vivo measurements.},

keywords = {In silico, in-silico, in-vitro, in-vivo, Pharmacokinetics, testing methods},

pubstate = {published},

tppubtype = {article}

}