Pharmacokinetic and toxicological assessment of a solid self-microemulsifying drug delivery system (S-SMEDDS) of kaempferia parviflora in rats

Abstract

Kaempferia parviflora (KP), renowned as an alternative medicine, has gained widespread acclaim for its efficacy in male sexual enhancement and anti-inflammatory applications. However, methoxyflavones, its primary compound, poses challenges due to inherent low water solubility and limited oral absorption. This study aims to develop a novel solid self-microemulsifying drug delivery system for KP (KPS-SMEDDS) and to investigate the pharmacokinetic profile and acute toxicity. The liquid self-microemulsifying drug delivery system for KP (KPL-SMEDDS) was formed by combining Neobee® M − 5 (90 %) with a mixture of surfactant (10 %) consisting of Kolliphor® EL and polyethylene glycol 400 in a ratio of 1:2. Consequently, the KPL-SMEDDS was transformed into a powdered form by employing Sipernat® 22S as an absorbent in a 1:1 ratio. The developed formulations were subsequently evaluated for their physicochemical properties, in vitro dissolution tests, and in vivo oral absorption in rats by using methoxyflavones as the markers for quantitation. The findings demonstrated that the use of KPL-SMEDDS and KPS-SMEDDS improved the dissolution rate of methoxyflavones in 0.1 N HCl in comparison to KP powder. Comparative analysis revealed that the KPS-SMEDDS exhibited a significantly higher maximum drug concentration (Cmax) and area under the curve (AUC) values in comparison to the conventional KP extract. Notably, the KPS-SMEDDS formulation at an oral dose of 250 mg/kg remarkably increased the bioavailability of polymethoxyflavones up to 2.7- to 3-fold. Furthermore, acute oral toxicity assessment revealed no statistically significant alterations in clinical observations or biochemical parameters. These compelling findings underlined the potential of the KPS-SMEDDS formulation to augment the absorption and bioavailability of methoxyflavones, establishing its safety as an oral supplement.