Peer-Reviewed Journal Details
Mandatory Fields
Jankovic S.;O'Dwyer P.;Box K.;Imanidis G.;Reppas C.;Kuentz M.
2019
September
European Journal of Pharmaceutical Sciences
Biphasic drug release testing coupled with diffusing wave spectroscopy for mechanistic understanding of solid dispersion performance
Validated
Optional Fields
Amorphous drug Biphasic dissolution test Colloids Diffusing wave spectroscopy Drug precipitation Microrheology Solid dispersion
137
2019 Elsevier B.V. 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 novel light scattering technique is highly promising for future biopharmaceutical research on supersaturating systems such as solid dispersions.
0928-0987
10.1016/j.ejps.2019.105001
Grant Details