Oral bioavailability enhancement of vinpocetine using self-microemulsifying drug delivery system containing long chain triglycerides: Preparation and in vitro/in vivo evaluation

Abstract

Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor solubility and extensive hepatic first-pass metabolism. In the present work, self-microemulsifying drug delivery systems (SMEDDS) employing long chain triglycerides (LCT) were successfully developed to increase vinpocetine’s solubility and reduce its hepatic first pass metabolism, thus enhancing its overall oral bioavailability. Maisine™35-1 was chosen as the lipid component in the formulated SMEDDS as it showed the maximal vinpocetine solubility within different LCT tested. Feasibility of obtaining SMEDDS, containing Maisine™35-1, together with Transcutol®HP and either Cremophor®EL or Tween 80, was evaluated using ternary phase diagrams. In vitro release studies performed in phosphate buffer of pH 7.4 illustrated that extent of vinpocetine release from SMEDDS was drastically higher than that obtained from commercial Cavinton® tablets. The industrial usefulness of the developed SMEDDS was evaluated regarding their moisture sorption isotherms when filled into gelatin capsules and stored at different relative humidity. Vinpocetine’s optimal SMEDDS did not induce gross changes in the gastrointestinal mucosa of rats at the investigated dose. Moreover, it significantly improved the relative oral bioavailability of vinpocetine compared to Cavinton® tablets. Accordingly, this study suggests that SMEDDS containing LCT under proper optimization and safety assessment can be effectively utilized for oral bioavailability enhancement of vinpocetine.