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Research unit coordinated by Prof. Luisa Montanari  

Permanent staff: Prof.ssa Paola Minghetti, Dott. Francesco Cilurzo, Dott.ssa Antonella Casiraghi, Dott.ssa Francesca Selmin, Dott.ssa Chiara G.M. Gennari

Research associated: Dott. Umberto Musazzi, Dott.ssa Silvia Franzé, Dott.ssa Ilaria Franceschini, Dott. Paolo Rocco.

 

Transdermal and transmucosal permeability of medicinal products, cosmetics and medical devices

The knowledge of permeability and the amount of drug accumulated in the skin and mucosae is of paramount importance in the development of medicinal products, cosmetics and medical devices intended for topical application. The research activity aims both to develop assays to predict the in vivo performances and evaluate the permeability of chemicals as well as the possible enhancement strategies. An assay to study the barrier properties of film forming medical devices is currently under development.

 

Design of bioadhesive drug delivery systems: transdermal patches and mucoadhesive dosage forms.

Among drug delivery systems, patches have been gained interest to deliver active ingredients intended for systemic, regional or topic absorption. The optimization of drug absorption, patch adhesion to the skin and physical stability of drugs within the matrix are the most critical steps to be carefully evaluated. Therefore the matrix components should be selected keeping in consideration their influence on the biopharmaceutical properties and adhesion of patches. The research is focused on the evaluation of the features of novel adhesive polymers in order to identify a platform to deliver active ingredients having different physical-chemical properties. As the skin adhesion is considered critical by regulatory agencies, an effort was made to establish methods to fully characterize the adhesive properties.

As stated by Pharmacopoeia, mucoadhesive dosage forms are intended to administer drugs in the buccal cavity in order obtain local or systemic activity. By using conventional dosage forms, the bioavability of drugs administered via the buccal mucosa is affected by their removal from the oral cavity following the swallowing. Mucoadhesive polymers allow prolonging the permanence time of dosage forms on the application site and localizing the drug release on the site of absorption. Nevertheless, the hydration of these polymers results in the formation of an outer gel layer and the increase in the size of tablets affects negatively patients’ compliance and in some cases the drug bioavailability. The research aims to develop new low-swellable mucoadhesive materials and evaluate different approaches to modulate both the dissolution rate of polymers and the drug release. The feasibility of preparing microspheres, films and tablets is evaluated in order to evidence the impact of process and formulation parameters on the performances of the dosage forms. The mechanisms responsible of polymer mucoadhesion are also investigated.

 

Formulation and characterization of semisolid preparations

Semisolid preparations are conventional dosage forms intended for the application on the skin or mucosae in order to obtain systemic, regional and local activity. Moreover they constitute cosmetics as well as medical devices. One of the most critical aspects in the development of a successful product is the evaluation of the drug permeation and its optimization in order to identify the skin layer reached by the permeant.

The research activity aims to pre-formulate, formulate and characterize semisolid preparations to be manufactured in industries or compounded in hospital pharmacy when a personalized therapy is required.

 

Fast-dissolving dosage forms for pharmaceutical and food use
The research activity deals with the preparation and evaluation of the physical stability of solid dispersions as well as the formulation of orodispersible films.

When solubility is an issue, the preparation of solid dispersions of a drug in inert and hydrosoluble carries represents a suitable approach in the attempt to increase its wettability and apparent dissolution rate. Spray-drying and freeze-drying are effective techniques to prepare solid dispersions. The morphology is characterized by scanning electron microscopy (SEM). The particle size distribution and superficial area are determined by light scattering and BET, respectively. The drug solid state and the possible interactions occurring between components are investigated by calorimetric analysis, namely DSC and TGA, FTIR, powder X-ray diffraction. The in vitro release tests are carried out in over saturation condition to discriminate the features of the selected carriers and drug/polymer ratio in terms of drug apparent solubility.

Orodispersible films are solid dosage forms supposed to disintegrate or dissolve in less than three minutes in the mouth. The disintegration of the film corresponds to complete drug release. For the first time allowed maltodextrin were proposed as excipient to design fast-dissolving films produced by casting and hot-melt extrusion. The current films are intended to vehicle foodstuff (i.e. flavors), cosmetics and drugs. The basic formulation can be modulated in order to load high payload of drugs. As the film dissolution occurs in few seconds when placed in the mouth, the high absorbing capacity of oral mucosae is exploited. Films are characterized in terms of disintegration time, mechanical properties, drug loading and drug release pattern.

 

Implants: microspheres, scaffolds and drug eluting stents.

The research activity deals with PLGA microspheres, fibroin scaffolds and drug eluting stents.

PLGA-based microspheres are one the most successful approach among controlled drug delivery systems intended for parenteral administration. Because of heat-sensitivity and physic-chemical properties of PLGA and, in several cases, loaded drugs, ionizing radiations represent the method of choice to comply the sterilization requirements. The research is focused on the evaluation of the influence of ionizing radiations on the stability of PLGA based-drug delivery systems and medical devices, taking also in account the physico-chemical characteristics of the loaded drug and the production process (i.e. spray-drying, freeze-drying and emulsion solvent/extraction evaporation).

In tissue engineering scaffolds are matrices mimicking the structure and morphological features of native extracellular matrix, which provides mechanical support and regulates cell adhesion, proliferation and differentiation. Regenerated silk fibroin from cocoons of the silkworm Bombyx mori has been widely studied in tissue engineering due to the combination of mechanical strength to versatility in processing and biocompatibility. Multiple material formats are available with fibroin, including films, fibers, nets, membranes, sponges, and fibers, to provide versatility in uses for the engineering and regeneration of both soft and hard tissues. Thanks to its molecular and superficial features, fibroin-based implants are very little inflammogenic.

The research project aims to investigate the feasibility of new composite materials made of fibroin and hydrophilic polymers in designing 2D- and 3D-scaffolds loaded by bioactive factors. To improve water stability of fibroin and, then, enhance mechanical properties of scaffolds, a final curing manipulating the secondary structure (i.e. the ratio between the β-sheets and random-coil regions) is required. Of particular interest is the preparation of 2D- and 3D-scaffolds by casting and freeze-drying, respectively and the evaluation of the effects on chemical and physic-chemical features of fibroin and loaded drugs after sterilization by vapor steam under pressure. The solid state, namely the ratio between the β-sheets and random-coil regions, is investigated by means of DSC, x-ray diffraction and ATR-FTIR spectroscopy. Concomitantly the influence of the blended polymer on chemical and physic-chemical properties of fibroin is evaluated. The in vitro degradation behavior of fibroin scaffolds in presence of proteolytic enzymes is studied in terms of the variation of the molecular weight distribution of fibroin and scaffold mechanical and morphological properties.

Activities on drug eluting stents are focused on the development of in vitro and/or ex vivo methods able to discriminate the formulative variables which can modulate in vivo local pharmacokinetic. The tests are intended to use both during R&D and QA controls.

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