Solid Self-Emulsifying Drug Delivery System (S-SEDDS) for Alpha-Lipoic Acid: A Novel Strategy to Enhance Solubility, Stability and Oral Bioavailability

Abstract

Alpha-lipoic acid (ALA) is a potent antioxidant with therapeutic potential in diabetic neuropathy, liver diseases, and neurodegenerative disorders. However, its clinical application is limited by poor water solubility and chemical instability, leading to reduced oral bioavailability. Initial studies revealed significant degradation of ALA approximately 30% under thermal stress and 17% in simulated gastric fluid (pH 1.2) and only 60% drug release in dissolution tests, underscoring its sensitivity to heat, acid and poor dissolution. To overcome these challenges, a Solid Self-Emulsifying Drug Delivery System (S-SEDDS) was developed using Medium-Chain Triglyceride (MCT) oil as the lipid phase, Cremophor RH 40 as surfactant, PEG 400 as co-surfactant and Neusilin UFL2 as the solid carrier. This formulation forms nanoemulsions upon contact with gastrointestinal fluids, enhancing solubility, stability and absorption. The optimized S-SEDDS demonstrated a significant increase in drug release, reaching 95.13% dissolution compared to 60% for pure ALA. Scanning Electron Microscopy (SEM) showed smooth, uniform particles, while Differential Scanning Calorimetry (DSC) confirmed conversion of crystalline ALA to an amorphous form, improving solubility. Drug content analysis confirmed 100% assay, indicating uniformity and stability. Stability studies under accelerated and ambient conditions over one month showed no significant changes in appearance, drug content or dissolution profile. These findings highlight S-SEDDS as a promising platform to enhance the delivery and therapeutic efficacy of ALA and other poorly soluble, unstable drugs