Mme Florence DUMAS - Nouvelle docteure de l'Université d'Angers

The December 1, 2020

Design of new formulations for BCS lll drugs encapsulation

Directeur de Thèse: Pr Jean-Pierre BENOIT

Co-directrice de Thèse : Dr Emilie ROGER

Abstract :

This work of thesis concerned the development of new microparticle formulation, enhancing the oral bioavailability of class III of biopharmaceutical classification system (BCS) drugs. This formulation is based on aqueous two-phase systems (ATPS), for oral administration. In the first part, ATPS composed of dextran and polyethylene oxide were characterized by phase diagram construction depending on polymers purity and form (liquid or powder). An easy one-step formulation process by dissolving a polymer mixture in powder form was suggested. Microparticles formulation was then developed from ATPS. ATPS were firstly stabilized based on Pickering method with chitosan-grafted lipid nanocapsules.
A gelled alginate shell was then formed by polyelectrolyte complexation. Systems obtained showed time stability (for 28 days) and with stood dilution and centrifugation. Finally, the study of insulin encapsulation in microparticles was initiated. However, due to low solubility of insulin at pH value for which microparticles are formulated (neutral pH), their encapsulation potential was not effectively evaluated. Despite the optimization opportunities remaining to be developed (especially for fitting them to molecules to encapsulate such as insulin), the systems formulated in this project appear promising for further BCS III oral administration.

Keywords : BCS lll, microparticles, oral administration, aqueous two-phase systems, insulin, Pickering