Investigating the influence of the type of polymer on sustaining the supersaturation from amorphous solid dispersions of Apremilast and its pharmacokinetics

Publication: J Drug Dev Sci and Tech
Software: GastroPlus®


Apremilast, a BCS class IV drug, has minimal solubility in aqueous medium which results in poor bioavailability. With an intention of enhancing the bioavailability, amorphous solid dispersions (ASDs) of Apremilast were developed and reported in our previous study. The purpose of this study emphasised on studying the impact of polymer type on sustaining supersaturation and maintaining stable ASDs of Apremilast. Besides, the study also investigated the moisture sorption of the ASDs at 75% relative humidity with respect to the stability and drug release and in vivo oral bioavailability assessment. The drug polymer miscibility was assessed with the aid of solubility parameter. The ASDs were then prepared with PVP, PVPVA, PEG, HPMCAS, Poloxamer, HPC and Soluplus (Drug: Polymer, 10:90) by quench cooling or solvent evaporation method. The produced solid dispersions were characterized using FTIR, DSC and XRD. Pharmacokinetic study of the optimised ASDs of Apremilast following oral delivery was performed in male Wistar rats. Solid state characterization exhibited amorphous nature of drug in the solid dispersions. The solubility and release study confirmed the enhancement of solubility of APR to an appreciable extent. The stress studies conducted also revealed that the polymers in the ASDs demonstrated good crystallisation inhibiting capacity by arresting the phase separation among the ASDs. Among the ASDs prepared, APR-PVP and APR-PVP VA exhibited higher drug release. As a result, APR-PVP and APR-PVP VA were optimised for the in-vivo study. The in vivo study showed that the Cmax of APR from ASDs was enhanced 2.5 fold, thus confirming the enhancement in oral bioavailability.

By Disha Shetty, Dani Lakshman Yarlagadda, Bheemisetty Brahmam, Swapnil J. Dengale, Shaila A. Lewis