Enhanced Delivery of Posaconazole Using Novel Solid Self Nanoemulsifying Drug Delivery System: In Vitro Characterization and Pharmacokinetic Study in Wistar Rats

Abstract

Purpose

Posaconazole (POS) is widely used as an antifungal agent effective against Candida infections. Because of its very low water and high fat solubility, it falls under the Biopharmaceutics Classification System (BCS) Class II. It showed considerable differences in absorption rates among individuals when administered orally. To overcome these obstacles, the current research concentrates on creating a solid self nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of POS to enhance its dissolution rate and bioavailability.

Methods

The choice of formulation components, Capmul MCM C8 as an oil, Tween 20 as a surfactant, and Acrysol K140 as a co-surfactant depended on their ability to solubilize POS and their capacity to form emulsions. Ternary phase diagrams were drawn to pinpoint and delineate the micro-emulsification region. The D-optimal mixture design was employed to facilitate the selection of the most optimized formulation by evaluating vital product characteristics including globule size, zeta potential, transparency percentage as well as emulsification efficiency. The optimized liquid SNEDDS (L-SNEDDS) was then converted into a solid state by employing Neusilin^® US2 as a porous carrier, improving the product’s stability and handling ease. The prepared formulation was further evaluated by in vitro and in vivo study.

Results

Examination of the S-SNEDDS structure through scanning electron microscopy showed spherical, granular particles, suggesting favourable flow characteristics. Dissolution tests conducted in vitro revealed that the rate of POS release from the S-SNEDDS was superior to that of unprocessed drug and marketed formulation. In vivo bioavailability study showed 2.27 and 1.96 fold higher bioavailability as compared to pure drug and marketed formulation respectively.

Conclusion

Present study revealed that the ability to self-emulsify was preserved when the L-SNEDDS was solidified. Further it demonstrated enhancement in dissolution and bioavailability of POS which depicted use of developed POS loaded S-SNEDDS for successful oral administration.