Development of a Sustained Release Dosage Form for α‐Lipoic Acid. I. Design and In Vitro Evaluation

Abstract

The purpose of this study was the design and evaluation of a sustained release dosage form for the oral administration of α‐lipoic acid. The cationic polymer chitosan was used in order to provide a controlled drug release based on ionic interactions with the anionic drug. The effect of such ionic interactions on the release of α‐lipoic acid could be verified by diffusion studies. In vitro release studies with tablets (diameter: 10.0 mm; thickness: ∼ 4 mm) containing 80% α‐lipoic acid and 20% chitosan acetate showed a controlled drug release over a time period of 24 h. Raising the ratio of chitosan acetate in such delivery systems led to an even stronger retardation of drug release. In addition, permeation studies carried out in Ussing‐type chambers with freshly excised intestinal mucosa from guinea pigs demonstrated no significant (p < 0.05) influence of the degree of drug ionization on its absorption behavior. The apparent permeability coefficient (P_app) for α‐lipoic acid was determined to be 1.39 ± 0.28 × 10^{− 5} cm/sec at pH 6.4 (means ± SD). The use of a sustained delivery system for α‐lipoic acid, which is based on ionic interactions, should therefore have no influence on the absorption behavior of the drug. The sustained release dosage forms described here might provide a constant plasma level of the drug being highly beneficial for various therapeutic reasons.

Key Words:

• α‐Lipoic acid
• Chitosan
• Controlled drug release
• Oral drug delivery
• Permeation studies

Acknowledgment

We thank Dr. O. Hoffmann and coworkers from the Institute of Pharmacology, University of Vienna, for the supply with small intestine of guinea pigs.