Analysis of the Enhanced Stability of R(+)-Alpha Lipoic Acid by the Complex Formation with Cyclodextrins

Abstract

R(+)-alpha lipoic acid (RALA) is one of the cofactors for mitochondrial enzymes and, therefore, plays a central role in energy metabolism. RALA is unstable when exposed to low pH or heat, and therefore, it is difficult to use enantiopure RALA as a pharma- and nutra-ceutical. In this study, we have aimed to stabilize RALA through complex formation with cyclodextrins (CDs). α-CD, β-CD and γ-CD were used for the formation of these RALA-CD complexes. We confirmed the complex formation using differential scanning calorimetry and showed by using HPLC analysis that complexed RALA is more stable than free RALA when subjected to humidity and high temperature or acidic pH conditions. Scanning electron microscopy studies showed that the particle size and shape differed depending on the cyclodextrin used for complexation. Further, the complexes of CD and RALA showed a different particle size distribution pattern compared with that of CD itself or that of the physical mixture of RALA and CD.

Isomeric effects of anti-diabetic α-lipoic acid with γ-cyclodextrin

“…Since the stability of αLA is affected by exposure to acid, ultraviolet light, or oxygen, the stabilization of R-αLA is important for its industrial use. A complex between αLA and γCD is known to be more stable in the stomach or intestines of a living body than free αLA [7]. We subsequently reported that the anti-diabetic effects of racemic-αLA/γCD were stronger than those of free racemic-αLA.…”

“…The preparation of αLA/γCD complexes was done as previously described [7]. R-, S-, or racemic-αLA was dissolved in deionized water, in which the pH was monitored, and a corresponding molar amount of γCD was added for a 1:1 ratio.…”

“…Takahashi et al demonstrated that racemic-αLA could be stabilized through the complex formation with γ-cyclodextrin (γCD) [23]. We have also recently reported that γCD stabilized R-αLA and yielded an R-αLA/γCD complex [7].…”

Development and characterization of a self-double-emulsifying drug delivery system containing both epigallocatechin-3-gallate and α-lipoic acid

“…The sample injection volume was 20 lL and mobile phase was at a flow rate of 1.2 mL/ min. The EGCG and ALA were detected by the wavelength of 280 and 215 nm, respectively, and the temperature of column oven was maintained at 30°C [32,33].…”

Physicochemical Characterization of Cyclodextrin–Drug Interactions in the Solid State and the Effect of Water on These Interactions

“…These complexes have been exploited to enhance material properties, especially the solubility, stability, and bioavailability of drugs. 12,[17][18][19]21,22 Over 35 different drugs are currently being marketed globally as solid or solution-based CD complex formulations. 20,23,24 Cyclodextrins form inclusion complexes with drug molecules in solution and solid states as described above, and the CDdrug inclusion complexes are well known to be prepared in the presence of water molecules.…”