Biphasic drug release testing coupled with diffusing wave spectroscopy for mechanistic understanding of solid dispersion performance.

Biphasic drug release testing coupled with diffusing wave spectroscopy for mechanistic understanding of solid dispersion performance. Eur J Pharm Sci. 2019 Jul 10;:105001 Authors: Jankovic S, O'Dwyer PJ, Box KJ, Imanidis G, Reppas C, Kuentz M Abstract Amorphous Solid dispersions (ASDs) represent an important formulation technique to achieve supersaturation in gastrointestinal fluids and to enhance absorption of poorly water-soluble drugs. Drug release from such systems is complex due to emergence of different colloidal structures and potential drug precipitation, which can occur in parallel to absorption. The latter drug uptake from the intestinal lumen can be simulated by an organic layer in a biphasic in vitro test, which was employed in this work to mechanistically study the release of ketoconazole from ASDs produced by hot melt extrusion using different HPMCAS grades. A particular aim was to introduce diffusing wave spectroscopy (DWS) to biopharmaceutical testing of solid dispersions. Results indicated that amorphous formulations prevented crystallization of the weakly basic drug upon transfer into the intestinal medium. Microrheological differences among polymer grades and plasticizers were revealed in the aqueous phase, which affected drug release and subsequently uptake into the organic layer. The results indicate that DWS can be employed as a new non-invasive tool to better understand drug release from solid dispersions. This...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research