Co-crystal integrity and pharmaceutical role of Cremophor ELP

Abstract

Co-crystals are sensitive to dissociation in aqueous microenvironment losing their effects on bioavailability increase before oral administration. The integrity of the fumaric acid co-crystal of SAR1 active pharmaceutical ingredient (API) was studied after a wet granulation process with four formulations containing the same qualitative and quantitative composition. Standard pharmaceutical excipients, particularly water and Cremophor ELP were used in different addition order to evaluate the robustness of the manufacturing process. Slight dissociation of fumaric acid co-crystal was measured by XRPD in all cases, lowest dissociation was observed when Cremophor ELP was added to the granulation liquid. Dissolution profiles of the formulations were analysed by flow through dissolution method. The in vitro dissolution profile of the experimental formulation showing the best co-crystal integrity was approximately 10% lower compared to the formulation with the highest integrity.