Development and Characterization of α-Lipoic Acid Amorphous Solid Dispersion for Improved Oral Bioavailability and Modulation of Allergic Airway Inflammation

Abstract

α-Lipoic acid (LA), a naturally occurring antioxidant and anti-inflammatory agent, has limited aqueous solubility and bioavailability which hinders its clinical application. To overcome these limitations, in this study, we have developed LA solid dispersion (LASD) using soluplus (SOL) to improve its oral bioavailability and therapeutic efficacy for modulating ovalbumin-lipopolysaccharide (OVA-LPS) induced allergic airway inflammation.

Highlights

The therapeutic potential of α-Lipoic acid (LA) is hindered due to its limited aqueous solubility and bioavailability.

LASD formulations have been developed and comprehensively characterized.

The developed LASD enhanced the dissolution rate and oral bioavailability of LA.

LASD demonstrated improved efficacy in OVA-LPS airway inflammatory model.

The LASD was prepared using lyophilization technique and optimized based on solid-state characterization. The developed SD has been comprehensively characterized using Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and powder X-ray diffraction (P-XRD) which confirmed the molecular dispersion of LA within the SOL matrix and its amorphous transformation.

The in vitro dissolution and pharmacokinetic studies revealed enhanced dissolution and oral bioavailability (5.3-fold) of LASD compared to native LA. The developed LASD significantly attenuated airway inflammation by reducing cytokine levels, major inflammatory markers and histopathological changes in lung tissues. Our study demonstrated that LASD formulation can be a promising strategy to overcome bioavailability as well as therapeutic efficacy challenges associated with LA.

Materials

α-Lipoic acid, PVP K 90, PVP K 30 and Kolliphor 407 were purchased from Sigma Aldrich (USA). Soluplus and Kollidon VA 64 was received as gift sample from BASF. All other reagents and solvents used were of analytical/HPLC grade.

Ruchika, Navneet Thakur, Narendra Vijay Tirpude, Ankit Saneja, Development and Characterization of α-Lipoic Acid Amorphous Solid Dispersion for Improved Oral Bioavailability and Modulation of Allergic Airway Inflammation, Colloids and Surfaces B: Biointerfaces, 2025, 114836, ISSN 0927-7765, https://doi.org/10.1016/j.colsurfb.2025.114836.