Alpha-lipoic acid (ALA) demonstrates significant therapeutic potential in obesity treatment and associated comorbidities, including diabetic neuropathy and hyperlipidemia. However, effective doses are high (up to 1800 mg daily) and are consequence of poor bioavailability, caused mainly by low solubility and gastrointestinal instability. This leads to high therapy costs and poor patient adherence. The goal of this study was to improve ALA solubility and stability using innovative pharmaceutical formulations based on cyclodextrin complexation.
In silico screening was used to identify cyclodextrins with the highest potential for enhancing ALA solubility. Experimental validation employing native cyclodextrins and hydroxypropylated derivatives involved phase solubility assessments, preparation of the complexes in the solid state followed by recovery and dissolution studies. Solid complexes were characterized using differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis.
Native cyclodextrins demonstrated limited potential for the enhancement of ALA solubility. In contrast, hydroxypropylated cyclodextrins, particularly hydroxypropyl-β-cyclodextrin, significantly improved its solubility and gastrointestinal stability. Complexation with hydroxypropyl-β-cyclodextrin yielded the most promising results in terms of solubility enhancement and dissolution profiles.
Conclusions: Cyclodextrin complexation, specifically with hydroxypropylated derivatives, presents an effective strategy to enhance the bioavailability of ALA. This approach could reduce the required daily dose for obesity treatment, improving patient adherence and reducing therapy costs. Cyclodextrin-based formulations represent a promising avenue for optimizing ALA’s therapeutic potential in obesity and its comorbid conditions.
Radić, K.; Miljak, K.; Jug, M.; Čepo, D. V.; Vianello, R.; Vrban, L. (2025) Improved Bioavailability of Alpha-Lipoic Acid Through Cyclodextrin Complexation: A Potential for Enhanced Obesity Treatment.
32nd European Congress on Obesity (ECO 2025) Obes Facts 2025;18(suppl 1):1–656. DOI:10.1159/000545547. Abstract book: PO1.119. https://karger.com/ofa/article-pdf/doi/10.1159/000545547/4375755/000545547.pdf