Thesis of Simon Samsoen

Defense of thesis of Simon Simsoen - laboratoire UMET

Abstract :

This thesis aims at improving our fundamental knowledge on the mechanisms involved in the formation of amorphous solid dispersions (ASD) of a drug within a polymer excipient, in particular the impact of the macromolecular architecture on the physical stability of ASD.
Poly(N-vinylpyrrolidone) (PVP) polymers with low dispersity and different molar masses and chain-end functionalities are first synthesised in a controlled manner by RAFT/MADIX (Reversible Addition-Fragmentation chain Transfer/ Macromolecular design by Interchange of Xanthates). They are then used to formulate, by co-milling and solvent evaporation processes, mixtures with curcumin (CUR). The advanced physico-chemical characterisation of PVP, CUR and the obtained ASD enables us to establish the CUR/PVP phase (solubility limit) and state (glass transition temperature (Tg) evolution) diagrams. On the one hand, this diagram allows us to better understand the stability conditions of CUR/PVP ASD and the impact of the PVP molar mass and chain-end functionality. On the other hand, comparison with ASD formulated with high dispersity commercial PVP allows us to highlight the specific role of the dispersity on the Tg of PVP and of CUR/PVP ASD. Indeed, for ASD formulated with high dispersity PVP, results show the decrease of Tg at high PVP contents, which unveils a competition between the development of attractive interactions between CUR and PVP and a plasticising effect induced by the broad distribution of PVP molar masses. Finally, this work reveals that the use of PVP synthesised in a controlled manner allows to obtain stable ASD over a broader range of temperatures and CUR concentrations than for ASD formulated with industrially available PVP of high dispersity.

Keywords : physical state,amorphous solid dispersions,structure and dynamic,stability,polyvinylpyrrolidone,glass-transition