FORMULATION DEVELOPMENT OF PVP-BASED SOLID DISPERSION OF LUMEFANTRINE WITH PIPERINE FOR SOLUBILITY ENHANCEMENT

The oral bioavailability of lumefantrine (LUMF) is low and erratic owing to its low aqueous solubility and P-glycoprotein (P-gp) mediated efflux. The present investigation aims to develop amorphous solid dispersions (SD) of LUMF co-loaded with piperine (PIP), a P-gp and CYP3A4 inhibitor, to improve its dissolution and thereby oral bioavailability. LUMF-SDs were prepared by using Polyvinyl-pyrrolidone, grade Povidone K30 (PVP) as a polymeric carrier, at three different ratios with increasing concentrations of polymer, employing melt method. DSC, XRD and FTIR characterized the PIP-LUMF-PVPSD at ratio of 1:6:18demonstrating higher aqueous solubility of LUMF. The DSC thermogram and XRD diffractogram confirmed the loss of crystallinity of both LUMF and PIP in PIP-LUMF SD, resulting in improved dissolution. Moreover, the possible molecular interactions between LUMF and PIP and /or PVP were investigated by FTIR studies. Crystallinity being a function of time, the stability of LUMF-PIP-PVP SD exposed to stressed humidity and temperature conditions (40 °C/75% RH) for 90 days was validated by DSC and release studies. These findings suggest that the SD of LUMF incorporated with P-gp inhibitor PIP improves dissolution and thereby could improve the bioavailability of LUMF.