@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{Caccavo2024b,

title = {Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets},

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

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145821046\&doi=10.1016%2fj.ces.2022.118371\&partnerID=40\&md5=d837f63862ad2ca8881845352400e79a},

doi = {10.1016/j.ces.2022.118371},

issn = {92509},

year  = {2024},

date = {2024-03-05},

journal = {Chemical Engineering Science},

volume = {267},

number = {118371},

abstract = {The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behavior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration.},

keywords = {case study, drug release, in-vitro stomach},

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}2023,

title = {Hydrogel: pH Role on Polyelectrolyte Behaviour in Aqueous Media},

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

doi = {10.3303/CET23100067},

issn = {22839216},

year  = {2023},

date = {2023-06-30},

journal = {Chemical Engineering Transactions},

volume = {100},

pages = {397-402},

abstract = {Polyelectrolytes are a class of polymer whose swelling depends on the external condition of pH. The dissociation of the ionizable groups is strongly depended on the concentration of the H+ ions in solution and this leads to different swelling behaviour changing the external pH. Since these materials are versatile and used in various fields, an in-depth knowledge of their behaviour becomes important to use them appropriately. The present work aims to offer an overview of the behaviour of these materials in solution through an experimental and a steady state modelling part. The results serve as a fundamental basis to understand the behaviour of these systems, including transient periods, leading to a comprehensive and predictable description.},

keywords = {Hydrogel, Polyelectrolyte Behaviour},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2023b,

title = {Coaxial Injection Mixer for the Continuous Production of Nanoparticles},

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

url = {https://doi.org/10.3303/CET23100051},

doi = {10.3303/CET23100051},

issn = {22839216},

year  = {2023},

date = {2023-06-30},

journal = {Chemical Engineering Transactions},

volume = {100},

pages = {Pages 301-306},

abstract = {Nanoparticles (NPs) production in batch reactors is limited in terms of reproducibility and control over physical properties such as particle size. Microfluidic techniques and flow-focusing can improve these limitations, but continuous nanoprecipitation through turbulent mixing can also be achieved. This study evaluates the effect of fluid dynamics on NP production and characteristics in a coaxial jet mixer. The results showed that the vertical and horizontal configurations of the mixer impact mixing performance, with buoyancy in the horizontal configuration causing fluid segregation and altering the coaxiality. The mixing performance was tested using water/water and ethanol/water systems with different flow rates, and results indicated that a turbulent jet develops at high values of both the Flow Momentum Ratio (FMR) and Reynolds number (NRe). The mixing time for the turbulent jet was found to have a clear relationship with the Reynolds number and FMR and was successfully fitted using a power law equation. Finally, the results showed that the NPs produced in turbulence were smaller and more uniform in size, with a Z-average half that of those produced in laminar conditions. The improved size uniformity and reduced dimensions of the particles resulted in a clearer final product. This study suggests that micromixing is a more favourable method for producing liposomes with improved characteristics and higher productivity compared to interdiffusion.},

keywords = {Coaxial Injection, Continuous Production, nanoparticles},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2023,

title = {Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets},

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

url = {https://www.sciencedirect.com/science/article/pii/S0009250922009563},

doi = {10.1016/j.ces.2022.118371},

year  = {2023},

date = {2023-03-05},

journal = {Chemical Engineering Science},

volume = {267},

abstract = {The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behavior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration.},

keywords = {Drug Delivery Systems, Mathematical modeling, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Iannone2022b,

title = {A low-cost push\textendashpull syringe pump for continuous flow applications},

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

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126485889\&doi=10.1016%2fj.ohx.2022.e00295\&partnerID=40\&md5=dc11ca55d5dc7a36fb1415ec58406b11},

doi = {10.1016/j.ohx.2022.e00295},

issn = {24680672},

year  = {2022},

date = {2022-04-11},

journal = {HardwareX},

volume = {11},

number = {e00295},

abstract = {Syringe pumps are very useful tools to ensure a constant and pulsation-free flow rate, however usability is limited to batch processes. This article shows an open-source method for manufacturing a push pull syringe pump, valid for continuous processes, easy to build, low-cost and programmable. The push-pull syringe pump (PPSP) is driven by an Arduino nano ATmega328P which controls a NEMA 17 in microstepping via the A4988 stepper driver. The Push-Pull Syringe Pump setup is configurable by means of a digital encoder and an oled screen programmed using C ++. A PCB was designed and built to facilitate the assembly of the device. The continuous flow is guaranteed by four non-return valves and a dampener, which has been sized and optimized for use on this device. Finally, tests were carried out to evaluate the flow rates and the linearity of the flow. The device is achievable with a cost of less than 100 €. },

keywords = {3D-printing, Continuous flow, Dual syringe pump, Push\textendashpull},

pubstate = {published},

tppubtype = {article}

}

@article{Iannone2022,

title = {A low-cost push\textendashpull syringe pump for continuous flow applications},

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

url = {https://www.sciencedirect.com/science/article/pii/S2468067222000402},

doi = {10.1016/j.ohx.2022.e00295},

year  = {2022},

date = {2022-04-01},

journal = {HardwareX},

volume = {11},

abstract = {Syringe pumps are very useful tools to ensure a constant and pulsation-free flow rate, however usability is limited to batch processes. This article shows an open-source method for manufacturing a push pull syringe pump, valid for continuous processes, easy to build, low-cost and programmable.



The push\textendashpull syringe pump (PPSP) is driven by an Arduino nano ATmega328P which controls a NEMA 17 in microstepping via the A4988 stepper driver. The Push-Pull Syringe Pump setup is configurable by means of a digital encoder and an oled screen programmed using C ++. A PCB was designed and built to facilitate the assembly of the device. The continuous flow is guaranteed by four non-return valves and a dampener, which has been sized and optimized for use on this device. Finally, tests were carried out to evaluate the flow rates and the linearity of the flow. The device is achievable with a cost of less than 100 €.},

keywords = {Instrumentation and control, New devices, Prototyping},

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{Caccavo2021,

title = {Dynamometric measurements of hydrogels' mechanical spectra},

author = {Diego Caccavo and Rosario Cavallo and Michela Abrami and Mario Grassi and Anna Angela Barba and Gaetano Lamberti},

url = {https://onlinelibrary.wiley.com/doi/full/10.1002/app.50702},

doi = {10.1002/app.50702},

year  = {2021},

date = {2021-03-12},

journal = {Journal of Applied Polymer Science},

volume = {138},

number = {50702},

abstract = {Hydrogels' viscoelastic behavior is crucial in several applications and an in‐depth knowledge and characterization of this property is essential to select the most appropriate gel for the specific use. Oscillatory shear measurements are the most commonly used techniques to perform the viscoelastic characterization of hydrogels, among other materials, and it is performed mainly by using plate‐plate shear rheometers. Despite these instruments constitute one of the best options to analyze the mechanical response of materials, they are quite expensive and require well trained operators, which confine their presence exclusively in engineering labs. However, the use of hydrogels brought these materials to be present in countless sectors, and therefore poses the need of reliable characterization with as much simple and common instrumentations. Therefore, aim of this work is to present the possibility to obtain a trustworthy characterization of the viscoelasticity of hydrogel by using a Texture Analyzer set to work with sinusoidal deformations.},

keywords = {Gels, Rheology, Viscosity and Viscoelasticity},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2021,

title = {Polymer\textendashLipid Pharmaceutical Nanocarriers: Innovations by New Formulations and Production Technologies},

author = {Sabrina Bochicchio and Gaetano Lamberti and Anna Angela Barba},

editor = {Thomas Rades},

url = {https://www.mdpi.com/1999-4923/13/2/198/htm},

doi = {10.3390/pharmaceutics13020198},

issn = {19994923},

year  = {2021},

date = {2021-02-02},

journal = {Pharmaceutics},

volume = {13(2)},

number = {198},

pages = {15},

abstract = {Some issues in pharmaceutical therapies such as instability, poor membrane permeability, and bioavailability of drugs can be solved by the design of suitable delivery systems based on the combination of two pillar classes of ingredients: polymers and lipids. At the same time, modern technologies are required to overcome production limitations (low productivity, high energy consumption, expensive setup, long process times) to pass at the industrial level. In this paper, a summary of applications of polymeric and lipid materials combined as nanostructures (hybrid nanocarriers) is reported. Then, recent techniques adopted in the production of hybrid nanoparticles are discussed, highlighting limitations still present that hold back the industrial implementation. },

keywords = {drug delivery, hybrid nanoparticles, lipids, nanotechnologies, polymers, production technologies},

pubstate = {published},

tppubtype = {article}

}

@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{Simone}2020b,

title = {Nanoliposomes in polymeric granules: Novel process strategy to produce stable and versatile delivery systems},

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

url = {https://www.sciencedirect.com/science/article/abs/pii/S1773224720311679?via%3Dihub},

doi = {10.1016/j.jddst.2020.101878},

year  = {2020},

date = {2020-07-09},

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

volume = {59},

pages = {7},

abstract = {Liposomes, due to their mimetic cellular composition, are gaining great attention as release systems for lipophilic and hydrophilic molecules. However, liposomes can present a high tendency to degrade and aggregate into biological fluids and under storage conditions. To overcome these limitations, in this work, a stabilizing strategy consisting in liposomes incorporation into polymeric granules was studied. Wet granulation was adopted to produce granules of hydroxypropyl methylcellulose (HPMC) and liposomal suspensions were used as the binder phase. In particular, in this study, three different percentages of liposome load in HPMC granules were investigated (1%, 5% and 10% w/w) focusing the attention on several relevant technological characteristics of the achieved solid particulates: size, flow index, mechanical strength (granules without liposomal inclusions were used as a control). Morphological observations (by TEM) confirmed the presence of intact liposomes in dry HPMC granules; moreover, it was found that the binder phase with the lower liposome concentrations (1%, 5%) did not significantly affect size, flowability and hardness of the lipid-polymer granules. Instead, the granules containing the highest percentage of liposomes (10% w/w) have larger dimensions, harder structure and reduced flowability. Therefore, the followed process strategy, under liposomal concentration restrictions, allowed to obtain both the liposomes stabilization, a not trivial technological issue, and the production of particulates with good solid state properties, useful as a versatile dosage form (lipid carriers in polymer carriers).},

keywords = {Compressibility index, Lipid-polymeric, Simil-microfluidic method, Texture analyses, Wet granulation},

pubstate = {published},

tppubtype = {article}

}

@article{Milocco2020,

title = {Thermal gelation modeling of a pluronic-alginate blend following coronary angioplasty },

author = {Alessio Milocco and Nicola Scuor and Vanni Lughi and Gaetano Lamberti and Anna Angela Barba and Rosario Divittorio and Gabriele Grassi and Andrea Perkan and Mario Grassi and Michela Abrami},

url = {https://onlinelibrary.wiley.com/doi/epdf/10.1002/app.48539},

doi = {10.1002/app.48539},

year  = {2020},

date = {2020-07-05},

journal = {Journal of Applied Polymer Science},

volume = {137},

number = {25},

pages = {10},

abstract = {To overcome the complications connected to the treatment of coronary atherosclerosis by means of percutaneous transluminal angioplasty followed by stent implantation, the in situ release of antiproliferative nucleic acid based drugs (NABD) seems a promising approach. For their fragile nature, NABD cannot be released from drug eluting stents but they need to be embedded in a soft gel coating the coronary wall (endoluminal gel paving). This article deals with the thermal fate, once in the catheter, of a polymer blend composed by pluronic, giving rise to a soft gel in water upon temperature rise, and alginate, a natural polysaccharide giving origin to a strong gel in the presence of divalent cations. Simulations reveal that while the formation of a pregel is rapidly achieved, the formation of a mature gel takes a much longer time with respect to the residence time of the polymer blend inside the catheter. },

keywords = {alginate-pluronic, coronary angioplasty, Mathematical modeling, restenosis},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2020b,

title = {Microwave Treatments of Cereals: Effects on Thermophysical and Parenchymal-Related Properties},

author = {Anna Angela Barba and Carlo Naddeo and Silvestro Caputo and Gaetano Lamberti and Matteo D'Amore and Annalisa Dalmoro},

url = {https://www.mdpi.com/2304-8158/9/6/711},

doi = {10.3390/foods9060711 },

year  = {2020},

date = {2020-06-01},

journal = {Foods},

volume = {9},

number = {6},

pages = {14},

abstract = {Dielectric heating is one of the most interesting techniques for pest disinfestation. However, most of the literature works give information about the ability of microwave treatments at different power-time conditions to kill insects; less is given about the analysis of matrices structural properties and heat transport. Accordingly, the aim of this work is to investigate the effect of microwave treatments, applied for pest disinfestation, on heat transport behavior and physical/structural properties, such as water uptake capability, mineral losses, texture change, and germination capability, of most consumed cereals in human diet, such as weak wheat, durum wheat, and corn. Two different radiative treatments were performed: one in time-temperature conditions capable of inactivating the weed fauna, and the other at high temperatures of ~150 °C, simulating uncontrolled treatments. Heat transport properties were measured and showed to keep unvaried during both effective and uncontrolled microwave treatments. Instead, grain physical properties were worsened when exposed to high temperatures (reduction of germination ability and texture degradation). The achieved results, on the one hand, provide new structural and heat transport data of cereals after microwave treatments, actually not present in the literature, and on the other, they confirm the importance of correctly performing microwave treatments for an effective disinfestation without affecting matrices physical properties and nutritional features.},

keywords = {cereals; dielectric properties, food sanitization, microwave heating, pest disinfestation, thermal properties},

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{Bochicchio2020b,

title = {Advances in Nanoliposomes Production for Ferrous Sulfate Delivery},

author = {Sabrina Bochicchio and Annalisa Dalmoro and Gaetano Lamberti and Anna Angela Barba},

editor = {MDPI},

url = {https://www.mdpi.com/1999-4923/12/5/445/pdf},

doi = {10.3390/pharmaceutics12050445},

year  = {2020},

date = {2020-05-11},

journal = {Pharmaceutics},

volume = {12},

number = {5},

pages = {445},

abstract = {In this study, a continuous bench scale apparatus based on microfluidic fluid dynamic principles was used in the production of ferrous sulfate-nanoliposomes for pharmaceutical/nutraceutical applications, optimizing their formulation with respect to the products already present on the market. After an evaluation of its fluid dynamic nature, the simil-microfluidic (SMF) apparatus was first used to study the effects of the adopted process parameters on vesicles dimensional features by using ultrasonic energy to enhance liposomes homogenization. Subsequently, iron-nanoliposomes were produced at different weight ratios of ferrous sulfate to the total formulation components (0.06, 0.035, 0.02, and 0.01 w/w) achieving, by using the 0.01 w/w, vesicles of about 80 nm, with an encapsulation efficiency higher than 97%, an optimal short- and long-term stability, and an excellent bioavailability in Caco-2 cell line. Moreover, a comparison realized between the SMF method and two more conventional production techniques showed that by using the SMF setup the process time was drastically reduced, and the process yield increased, achieving a massive nanoliposomes production. Finally, duty-cycle sonication was detected to be a scalable technique for vesicles homogenization. },

keywords = {drug delivery, ferrous sulfate, nanoliposome, simil-microfluidic apparatus, sonication},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2020,

title = {Simil-Microfluidic Nanotechnology in Manufacturing of Liposomes as Hydrophobic Antioxidants Skin Release Systems},

author = {Sabrina Bochicchio and Annalisa Dalmoro and Veronica De Simone and Paolo Bertoncin and Gaetano Lamberti and Anna Angela Barba},

url = {https://www.mdpi.com/2079-9284/7/2/22/pdf},

doi = {10.3390/cosmetics7020022},

year  = {2020},

date = {2020-04-03},

journal = {Cosmetics},

volume = {7},

number = {22},

pages = {13},

abstract = {Novel nanotechnologies represent the most attractive and innovative tools to date exploited by cosmetic companies to improve the effectiveness of their formulations. In this context, nanoliposomes have had a great impact in topical preparations and dermocosmetics, allowing the transcutaneous penetration and absorption of several active ingredients and improving the stability of sensitive molecules. Despite the recent boom of this class of delivery systems, their industrial production is still limited by the lack of easily scalable production techniques. In this work, nanoliposomes for the topical administration of vitamin D3, K2, E, and curcumin, molecules with high antioxidant and skin curative properties but unstable and poorly absorbable, were produced through a novel simil-microfluidic technique. The developed high-yield semi continuous method is proposed as an alternative to face the problems linked with low productive conventional methods in order to produce antioxidant formulations with improved features. The novel technique has allowed to obtain a massive production of stable antioxidant vesicles of an 84\textendash145 nm size range, negatively charged, and characterized by high loads and encapsulation efficiencies. The obtained products as well as the developed high-performance technology make the achieved formulations very interesting for potential topical applications in the cosmetics/cosmeceutical field. },

keywords = {antioxidants, cosmeceutics, nanoliposomes, simil-microfluidic technology, transdermal delivery},

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{Lamberti2020,

title = {Drug Delivery of siRNA Therapeutics},

author = {Gaetano Lamberti and Anna Angela Barba},

url = {https://www.mdpi.com/1999-4923/12/2/178/pdf},

doi = {10.3390/pharmaceutics12020178},

year  = {2020},

date = {2020-02-20},

journal = {Pharmaceutics},

volume = {12(2)},

number = {178},

keywords = {aptamers, Drug Delivery Systems, gene therapy, liposomes, nanoparticles, polycations, siRNA},

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{Barba2019b,

title = {Coating of Nanolipid Structures by a Novel Simil-Microfluidic Technique: Experimental and Theoretical Approaches },

author = {Anna Angela Barba and Sabrina Bochicchio and Paolo Bertoncin and Gaetano Lamberti and Annalisa Dalmoro},

url = {https://www.mdpi.com/2079-6412/9/8/491/htm},

doi = {10.3390/coatings9080491},

year  = {2019},

date = {2019-08-02},

journal = {Coatings},

volume = {9},

number = {491},

pages = {1-15},

abstract = {Nanolipid vesicular structures are ideal candidates for the controlled release of various ingredients, from vitamins for nutraceutical purposes to chemoterapic drugs. To improve their stability, permeability, and some specific surface properties, such as mucoadhesiveness, these structures can require a process of surface engineering. The interaction of lipid vesicles with oppositely charged polyelectrolytes seems to be an interesting solution, especially when the negatively charged liposomes are complexed with the cationic chitosan. In this work, a novel simil-microfluidic technique was used to produce both chitosan-coated vesicles and a vegan alternative composed of cholesterol-free liposomes coated by Guar Hydroxypropyltrimonium Chloride (Guar-HC). The combination between the experimental approach, based on experimental observations in terms of Z-potential, and size evolutions, and the theoretical approach, based on concepts of saturation, was the methodology applied to define the best polycation concentration to fairly cover (vegan or not) liposomes without aggregation. The smart production of coated nanolipid structures was confirmed by characterizations of morphology, mucoadhesiveness, and stability.},

keywords = {Chitosan, Coated nanoliposomes, Guar guam, Liposome bioadhesive, Liposomi bioadesivi, Muchoadesiveness, Simil-microfluidic technique},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2019,

title = {Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications},

author = {Anna Angela Barba and Sabrina Bochicchio and Annalisa Dalmoro and Gaetano Lamberti},

url = {https://www.mdpi.com/1999-4923/11/8/360},

doi = {10.3390/pharmaceutics11080360},

year  = {2019},

date = {2019-07-24},

journal = {Pharmaceutics},

volume = {11},

number = {360},

abstract = {In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming “the latest generation medicine” with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugs},

keywords = {clinical trials, liposomes, Micro and Nano Vectors, NABDs, siRNA},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2019,

title = {Micronutrients encapsulation in enhanced nanoliposomal carriers by a novel preparative technology },

author = {Annalisa Dalmoro and Sabrina Bochicchio and Gaetano Lamberti and Paolo Bertoncin and Barbara Janssens and Anna Angela Barba},

url = {https://pubs.rsc.org/en/content/articlelanding/2019/ra/c9ra03022k},

doi = {10.1039/C9RA03022K},

year  = {2019},

date = {2019-06-25},

journal = {RSC Advances},

volume = {9},

pages = {19800-19812},

abstract = {Micronutrients administration by fortification of staple and complementary foods is a followed strategy to fight malnutrition and micronutrient deficiencies and related pathologies. There is a great industrial interest in preparation of formulations for joint administration of vitamin D3 and vitamin K2 for providing bone support, promoting heart health and helping boost immunity. To respond to this topic, in this work, uncoated nanoliposomes loaded with vitamin D3 and K2 were successfully prepared, by using a novel, high-yield and semi continuous technique based on simil-microfluidic principles. By the same technique, to promote and to enhance mucoadhesiveness and stability of the produced liposomal structures, chitosan was tested as covering material. By this way polymer\textendashlipid hybrid nanoparticles, encapsulating vitamin D3 and vitamin K2, with improved features in terms of stability, loading and mucoadhesiveness were produced for potential nutraceutical and pharmaceutical applications.},

keywords = {Drug Delivery Systems, Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Simone}2019,

title = {Effect of binder and load solubility properties on HPMC granules produced by wet granulation process},

author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/pii/S1773224718311043},

doi = {10.1016/j.jddst.2018.12.030},

year  = {2019},

date = {2019-02-01},

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

volume = {49},

pages = {513-520},

abstract = {Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.},

keywords = {Granulation, HPMC},

pubstate = {published},

tppubtype = {article}

}

@article{Simone}2018b,

title = {Wet-granulation process: phenomenological analysis and process parameters optimization},

author = {Veronica {De Simone} and Diego Caccavo and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/pii/S0032591018307800},

doi = {10.1016/j.powtec.2018.09.053},

year  = {2018},

date = {2018-12-01},

journal = {Powder Technology},

volume = {340},

pages = {411-419},

abstract = {Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000\textendash10,000 μm) as the main variable of interest.},

keywords = {Granulation, HPMC},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2018,

title = {Design and production of hybrid nanoparticles with polymeric-lipid shell\textendashcore structures: conventional and next-generation approaches},

author = {Sabrina Bochicchio and Annalisa Dalmoro and Paolo Bertoncin and Gaetano Lamberti and Rouslan I. Moustafine and Anna Angela Barba },

url = {https://pubs.rsc.org/en/Content/ArticleLanding/2018/RA/C8RA07069E#!divAbstract},

doi = {10.1039/c8ra07069e},

year  = {2018},

date = {2018-09-27},

journal = {RSC Advances},

volume = {8},

pages = {34614\textendash34624},

abstract = {Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Despite

their high biocompatibility, biodegradability and low intrinsic toxicity, their poor stability in biological fluids

as well as in stock conditions (high tendency to degrade or aggregate) have led to new approaches for

liposome stabilization (e.g., surface covering with polymers). Here, liposomes were enwrapped by the

natural biocompatible polymer chitosan to achieve stable shell\textendashcore nanostructures. Covered

nanoliposomes were produced using an innovative continuous method based on microfluidic principles.

The produced hybrid polymeric-lipid nanoparticles were characterized in terms of structural properties,

size and stability. Moreover, phenomenological aspects in formation of nanoliposomal vesicles and

chitosan layering, product quality (structure, size) and manufacturing yield related to this novel method

were compared with those of the conventional dropwise method and the obtained products. The

proposed simil-microfluidic method led to the production of stable and completely chitosan-covered

liposomes with a shell\textendashcore nanostructure that avoided the disadvantages inherent in the conventional

method (which are time-consuming and/or require bulky and more expensive equipment).},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2018b,

title = {Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems},

author = {Annalisa Dalmoro and Sabrina Bochicchio and Shamil F. Nasibullin and Paolo Bertoncin and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},

url = {https://www.sciencedirect.com/science/article/pii/S0928098718302331},

doi = {10.1016/j.ejps.2018.05.014},

year  = {2018},

date = {2018-08-30},

journal = {European Journal of Pharmaceutical Sciences},

volume = {121},

pages = {16-28},

abstract = {Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity.



Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods.



The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin.



Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.},

keywords = {Micro and Nano Vectors},

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{Dalmoro2018,

title = {On the relevance of thermophysic characterizations in microwave treatments of legumes},

author = {Annalisa Dalmoro and Carlo Naddeo and Silvestro Caputo and Gaetano Lamberti and Liberata Guadagno and Matteo D'Amore and Anna Angela Barba},

url = {http://pubs.rsc.org/en/Content/ArticleLanding/2018/FO/C7FO01488K},

doi = {10.1039/C7FO01488K},

issn = {2042-650X},

year  = {2018},

date = {2018-03-01},

journal = {Food \& Function},

volume = {9},

number = {3},

pages = {1816-1828},

abstract = {This study is focused on the characterization of thermal behavior and physical properties of most consumed legumes in daily diet such as beans, lentils and chickpeas. Because of a lack of knowledge in literature about the effect of microwave treatments on legumes, characterization protocols have been applied before and after subjecting them to microwave irradiation suitable for pest disinfestation. The effects of two different radiative treatments, one suitable to inactivate the infesting fauna, and one simulating uncontrolled treatments, characterized by very high temperatures, were tested. The impacts of microwave treatments on legumes, in terms of thermal behavior, germination capability, tannin and total polyphenols composition and other physical properties (water uptake capability, texture change, mineral losses), after typical soaking cooking processes, are also performed. Examined legumes thermal properties were found comparable for all samples. Similarly, no significative differences in antinutritional factors, polyphenols and tannins, content among all samples were detected. Under structural point of view, samples exposed to high temperatures have been shown a texture degradation and in turn, losses of mineral nutrient during soaking processes. Moreover, their germinative capability was drastically reduced. These latter results highlighted how is important to correctly perform radiative microwave process in order to both assure an effective and safe disinfestation and avoid nutritional values losses and physical properties worsening.},

keywords = {legumes, microwave, Tecnagri, thermophysic},

pubstate = {published},

tppubtype = {article}

}

@article{{DeSimone}2018,

title = {HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties},

author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba },

url = {http://www.sciencedirect.com/science/article/pii/S0144861717313425},

doi = {10.1016/j.carbpol.2017.11.056},

year  = {2018},

date = {2018-02-01},

journal = {Carbohydrate Polymers},

volume = {181},

pages = {939-947},

abstract = {Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various  elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45\textendash2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45\textendash2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.},

keywords = {Granulation},

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 = {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{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{Bochicchio2017b,

title = {On the design of tailored liposomes for KRX29 peptide delivery },

author = {Sabrina Bochicchio and Marina Sala and Antonia Spensiero and Maria Carmina Scala and Isabel Gomez-Monterrey and Gaetano Lamberti and Anna Angela Barba },

url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ03115G},

doi = { 10.1039/C7NJ03115G},

issn = {1144-0546},

year  = {2017},

date = {2017-12-01},

journal = {New Journal of Chemistry},

volume = {41},

number = {19},

pages = {11280-11290},

abstract = {The high interest in therapeutic peptides, due to the specificity of their mechanisms of action, has stimulated the research of new delivery strategies to overcome bioavailability problems concerning the use of peptides in their naked form. In particular, in this study, a novel small cyclic peptide, the KRX29, with a potential therapeutic effect on Heart Failure (HF) pathology, was encapsulated into large and unilamellar small vesicles (LVs, SUVs) by the thin film-hydration method followed by ultrasound assisted size reduction processes, generating loaded liposomes with nanometric sizes. Loaded and unloaded liposomes were produced exploring three different formulations by changing the charge ratio (-/+) between the anionic phosphatidylglycerol (PG) and the cationic KRX29 peptide. LVs and SUVs were designed using a 1:1, 7:1 and 13:1 (-/+) PG/KRX29 charge ratio and, for each formulation, the charge effect on liposomes morphology, size and zeta potential were analyzed together with peptide encapsulation performance, load, recovery efficiencies and stability through an analytical HPLC protocol purposely developed. Best results in terms of encapsulation in nanoliposomal formulation for KRX29 delivery, were achieved using a 13:1 (-/+) charge ratio (99 % in 35 nm SUVs). The influence of PG/KRX29 charge ratio on the recovery efficiencies was also investigated obtaining that the maximal peptide recovery from liposomes (81 \textendash 94 %) was achieved by using a 1:1 (-/+) charge ratio formulation and pure ethanol as solvent for the extraction.},

keywords = {liposome, peptide},

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{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{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{Simone}2017,

title = {Central Composite Design in HPMC granulation and correlations between product properties and process parameters},

author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},

url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ01280B#!divAbstract},

doi = {10.1039/C7NJ01280B},

year  = {2017},

date = {2017-07-21},

journal = {New Journal of Chemistry},

volume = {41},

number = {14},

pages = {6504-6513},

abstract = {Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production.},

keywords = {Granulation, HPMC},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2017,

title = {PoroViscoElastic model to describe hydrogels' behavior},

author = {Diego Caccavo and Gaetano Lamberti},

url = {http://www.sciencedirect.com/science/article/pii/S0928493116325760},

doi = {10.1016/j.msec.2017.02.155},

year  = {2017},

date = {2017-07-01},

journal = {Materials Science and Engineering: C},

volume = {76},

pages = {102\textendash113},

abstract = {Hydrogels are three-dimensional, cross-linked hydrophilic polymeric network able of absorb large amount of water. The mechanics of these systems is strictly coupled with the water transport resulting in the peculiar behavior known as poroviscoelasticy. This can be considered as sum of the viscoelastic behavior of the polymeric network and the poroelastic behavior caused by the water movement within the hydrogel. In this work a 3D monophasic model able to depict the poroviscoelastic behavior of these systems, within the field of nonlinear solid mechanics, is developed. The mass and momentum balances equations, supported by constitutive equations from non-equilibrium thermodynamics and by initial and boundary conditions, is implemented through the weak formulation in a commercial FEM-based software. A parametric study is performed in order to assess the relative importance of the model parameters on hydrogels' behavior.},

keywords = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}