Development and Optimization of Phospholipid-Based Efavirenz Nanosuspension for Enhanced Solubility and Lipolytic Performance

Abstract

Efavirenz (EFV), a BCS Class II antiretroviral drug, exhibits poor aqueous solubility, resulting in limited oral bioavailability. The present study aimed to develop and optimize a phospholipid-based nanosuspension of EFV using the antisolvent precipitation method to enhance its solubility and dissolution characteristics. Various stabilizers, including phospholipids, surfactants, and polymers, were screened to obtain a stable nanosuspension. A 2³ factorial design was employed to optimize the formulation by evaluating the effects of phospholipid load, surfactant concentration, and drug load on particle size and polydispersity index (PDI). The optimized formulation exhibited a particle size of 188.8 nm and a PDI of 0.115, indicating the formation of a stable and homogeneous nanosuspension. Morphological characterization was performed using transmission electron microscopy, while particle size analysis was conducted using dynamic light scattering. In vitro lipolysis studies demonstrated a significant improvement in EFV solubilization from the phospholipid–Tween 80 nanosuspension (PL-T-NS) compared to the conventional EFV dispersion. After 60 minutes of lipolysis, the optimized nanosuspension achieved 24.50 ± 0.42% drug solubilization, whereas the EFV dispersion showed only 5.58 ± 0.39% solubilization. The enhanced performance was attributed to the presence of phospholipids and the nanosized drug particles, which improved the formation of solubilizing colloidal structures during lipid digestion. The study demonstrates that phospholipid-based nanosuspensions represent a promising strategy for improving the solubility and oral delivery of poorly water-soluble drugs such as efavirenz.

Keywords: Efavirenz, Nanosuspension, Antisolvent Precipitation, Factorial Design, In Vitro Lipolysis