Shrawan Baghel
Waterford Institute of Technology, Ireland
Title: Investigating the dissolution performance of dipyridamole and cinnarizine spray dried amorphous solid dispersion using proton NMR
Biography
Biography: Shrawan Baghel
Abstract
Amorphous Solid Dispersions (ASDs) are of great interest as enabling formulations because of their ability to increase
the bioavailability of poorly soluble drugs. However, the dissolution of these ASD based formulations results in highly
supersaturated drug solution that can undergo different types of phase transition. We have investigated the dissolution
performance of amorphous solid dispersions of poorly water-soluble dipyridamole (DPM) and cinnarizine (CNZ) spraydried
amorphous solid dispersions (ASDs) using polyvinyl pyrrolidone (PVP) and polyacrylic acid (PAA) as a carrier matrix.
Dissolution studies were carried out under non sink conditions and solution phase drug-polymer interactions was characterized
using proton NMR. It was found that the dissolution of ASDs led to sustained supersaturation, the duration of which varied
depending on the drug loading and type of polymer used in the formulation. The main mechanism for drug supersaturation
generation and prolongation was found to be anti-plasticization effect of polymers on amorphous drugs within spray dried
ASDs and the ability of polymers to reduce the crystal growth rates of DPM and CNZ. To further understand the molecular
mechanism behind supersaturation stabilization in the presence of polymer, we employed, Solution 1H NMR. The change
in electron densities of proton and the relative intensities of peak shifts indicated the nature of interaction between drug and
polymer in different systems are different. These different effects suggest that DPM and CNZ interacts in a different way with
PVP and PAA in solution which goes some way towards explaining the different polymeric effect, particularly in terms of
inhibition of drug recrystallization and dissolution of DPM and CNZ ASDs. . The overall supersaturation profile observed thus
depended on a complex interplay between dissolution rate, polymer type, drug loading, crystallization mechanism of drugs
and drug-polymer interaction in the solution state.