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.