Permeation kinetics studies of physical mixtures of artemisinin in polyvinylpyrrolidone

Abstract

Artemisinin (ART), the parent compound of a novel family of antimalarial drugs, was used as a model drug that is lipophilic and has low bioavailability (32%) after oral delivery. The primary objective was to study the effect of polyvinylpyrrolidone (PVP) on the permeation enhancement and solubility of physical mixtures (PM) of ART in PVP-K30 in various solvent systems (i.e., distilled water, phosphate buffered saline [PBS], and methanol). PMs of drug-PVP in 1:0.5, 1:1, 1:2, 1:4, and 1:9 ratios were prepared by simple mixing in a mortar and pestle. Fourier transform infrared (FTIR) spectrophotometry and X-ray powder diffraction (XRPD) were applied to characterize the PMs. The solubility of ART was investigated at 37 ± 0.5 °C in three solvents. Permeation of ART-saturated solutions across a silicone membrane in Franz diffusion cells was studied using Fick's law of diffusion. FTIR and XRPD studies have shown some interactions, and there was a phase change of artemisinin from crystalline to amorphous form as the concentration of PVP-K30 in PM ratios increased. Solubility order increased with an increase in PVP- K30 concentration for the water-PBS solvent system, while in methanol, it was erratic. Flux rate and permeability coefficient were enhanced with an increase in PVP-K30 concentration. In less permeable solvents like water and PBS, the enhancement ratio was high, while the enhancement ratio was low in a highly permeable solvent like methanol. In conclusion, with an increase in concentration of PVP, the permeation rate and solubility of ART increased.