Track: Formulation and Delivery - Chemical - Formulation - Amorphous and Co-crystal Systems
Category: Poster Abstract
Counterions Facilitate High Drug Loading in Amorphous Solid Dispersion
Purpose: Amorphous solid dispersion is a powerful approach for delivering poorly water soluble drugs. However, high drug loading of ASDs are challenging with respect to physical stability and drug release, which limits the maximum dose and the achievement of the desirable high exposure. In this work, counterions were incorporated with API model compound indomethacin (IMC), to ionize the API and influence the pH of the diffusion layer. Improvement of dissolution rate was systemically studied to show the facilitating effect of counterions in high drug load ASDs. Methods: ASD of IMC, PVPVA and different counterions were prepared with solvent evaporation method using rotavap. IMC ionization status was characterized with Raman and ssNMR. Intrinsic dissolution rate studies were conducted using stationary disk method and samples were analyzed by high performance liquid chromatography (HPLC). Results: Intrinsic dissolution rate was significantly enhanced in the amorphous solid dispersion of IMC with Na and Tris counterions. Incorporating counterions into ASD increased intrinsic dissolution rate more than the corresponding physical mixtures. The enhancement effect was related to the ionization status of API in the ASDs and depended upon the molar ratio of API to counterions. Conclusion: Incorporating counterions could effectively improve the dissolution rate of ASDs of IMC. This enhancement could facilitate the high drug loading ASD formulation. Dissolution enhancement is related to the ionization effect of counterions, the molar ratio of API to counterions, and mechanism of incorporating of counterions. These findings can help better design high drug load ASD using counterions for ionizable drugs.