Development of Mefenamic Acid-Soluplus ® amorphous dispersions via hot melt extrusion and in silico prediction of oral absorption

Authors: Chavero E, Kurowska A, Lewis SA
Publication: Acta Pharm Sci
Keywords: ASD, biopharmaceutics, enabled formulations, gastroplus, pbbm, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Abstract

The objective of this study was to increase the solubility of Mefenamic Acid (MA), a BCS class II drug by formulating amorphous solid dispersions via Holt-Melt Extrusion. The extrudates were prepared at different drug to polymer ratios and characterised by standard analytical techniques. Dissolution studies were performed in Phosphate buffer saline (PBS) pH 7.4 medium. Stability of the different ratios of MA: Soluplus (1:1, 1:4 and 4:1) was studied at room temperature for 12 months. Computer simulation using GastroPlusTM was run to depict the gastrointestinal absorption of MA in humans. DSC thermograms and the diffractograms of the solid dispersions confirmed amorphous nature. Dissolution studies showed enhanced dissolution rate of MA from the solid dispersions. Stability studies indicated 1:4 (MA: Soluplus®) dispersion as the most stable dispersion. GastroPlus? simulation using in vitro data showed improvement in the PK parameters of the solid dispersión in comparison with pure MA.

By Estrella Chavero, Aleksandra Kurowska & Shaila A Lewis