@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{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},

urldate = {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},

urldate = {2020-03-31},

journal = {International Journal of Pharmaceutics},

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

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

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

pubstate = {published},

tppubtype = {article}

}

@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{{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{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}

}