Development of a Sustained Release Dosage Form for α‐Lipoic Acid. II. Evaluation in Human Volunteers

Abstract

Within this study an oral sustained release dosage form of α‐lipoic acid (thioctic acid) has been generated and evaluated in healthy volunteers. A granulate comprising 56.8% α‐lipoic acid and 43.2% chitosan acetate was compressed to tablets (weight: 0.45 g; diameter: 10.0 mm; thickness: 4 mm). Three of these tablets were administered at once orally to each volunteer. Prior to administration and then every hour for 12 hours blood samples were taken from the antebrachial vein. α‐Lipoic acid concentrations in plasma were quantified via precolumn derivatization and reversed‐phase high‐performance liquid chromatography (HPLC). Results demonstrated that an increased plasma level of α‐lipoic acid can be achieved by this formulation for at least 12 hours. Within this time period at least two maximum plasma concentrations were reached. The first one is based on the release of α‐lipoic acid, which is not ionically and therefore only loosely bound to chitosan, whereas a second maximum is based on the release of the drug during the enzymatic degradation of the chitosan matrix in the colon. The AUC_0→12 was determined to be 183.8 ± 101.4 µg × min/mL (mean ± SD; n = 8). Because of the pulsed sustained release of α‐lipoic acid, the dosage form described here seems to be highly beneficial in order to stimulate the glucose uptake in the case of diabetes type II.

Key Words:

• α‐Lipoic acid
• Chitosan
• Controlled drug release
• Diabetes
• Oral drug delivery