Lumefantrine Solid Dispersion Formulation Development and Characterization with Piperine for Solubility Enhancement

Abstract

Lumefantrine's limited water solubility and variable bioavailability are linked to its crystallinity and efflux mediated by P-glycoprotein (P-gp). Here, amorphous solid dispersions (SD) of lumefantrine (LUMF) including piperine (PIP), a P-gp and CYP3A4 inhibitor, were produced using Copovidone/Kollidon® VA 64 (KOL) at three different ratios with increasing polymer content in order to increase the dissolution and, therefore, the oral bioavailability. Using DSC, FTIR, and XRD, the PIP-LUMF-KOL SD at a ratio of 1:6:18 showed increased aqueous solubility of LUMF. While FTIR tests looked into potential intermolecular interactions between LUMF and PIP and/or KOL, the DSC thermogram and XRD diffractogram of LUMF-PIP-SD validated the enhanced dissolving brought on by LUMF's loss of crystallinity. The stability of LUMFPIP-Sol SD under stressful temperature and humidity conditions for 90 days was confirmed by DSC and dissolving studies. Overall, the findings point to the possibility that increasing the SD of LUMF combined with P-gp inhibitor PIP may improve solubility and, in turn, increase LUMF's bioavailability.