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.

Effect of Permeation Enhancers on the Release Behavior and Permeation Kinetics of Novel Tramadol Lotions

“…It has been suggested that the mechanism of skin permeation enhancement by PG occurs through the extraction of lipids from the SC layers [6,7,16]. PEG due to its solublizing properties is considered a good skin permeation enhancer, and when other lipophilic and hydrophilic surfactants are incorporated with it in formulations, enhances solubility and reduces hepatic metabolism by forming chylomicrons that uncrease lymphatic delivery, resulting in increased bioavailability [17].…”

“…In vitro permeation studies of TRA lotions across rabbit skin were carried out using two-chambered Franz-type diffusion cells (manufactured "in house") [6] having a receptor phase of ~5 ml, and a diffusional area of ~0.788 cm Bahauddin Zakariya University, Multan, Pakistan, this study was conducted in accordance with the international guidelines for animal use in laboratory experimentation [13]. Adult rabbit skin was used for permeation studies at 37 ± 0.5 o C. Abdominal full thickness skin of male White New Zealand rabbit (3 -4 kg weight) was carefully excised after sacrificing the rabbit.…”

“…Subcutaneous fats and other extraneous tissues adhering to the dermis were completely removed and trimmed with forceps and scissor. The skin was cleaned with phosphate buffered saline (PBS) at pH 7.4 and stored in 500 ml normal saline in a refrigerator (18 -20 o C) [6,7].…”

“…The concept of percutaneous absorption of drugs was given by Stoughton in 1965 [4). TDDS provides various merits over conventional drug delivery systems such as oral and parenteral delivery, including avoidance of hepatic first pass metabolism, reduction of pain, and possible sustained release of drugs [5][6][7].…”