Inclusion Complex of alpha-Lipoic Acid Containing Alkalizer for Improving the Solubility and Stability Prepared by Co-grinding

Abstract

The inclusion complex was prepared by co-grinding α-lipoic acid with hydroxypropyl-β-cyclodextrin and alkalizer to enhance the solubility and stability of α-lipoic acid. Lipoic acid was chosen as a model drug because of its poor and pH-dependent aqueous solubility. Sodium carbonate and sodium bicarbonate were chosen as the pH regulators. Furthermore, the study investigated the proportion of alkalizer, hydroxypropyl-β-cyclodextrin and α-lipoic acid. Although the micronization has little effect on the solubility of the drug, the formation of amorphous form has an important effect of inclusion complexes. X-ray powder diffractometry and differential scanning calorimetry were used to assess the phase change of the drugs. The in vitro dissolution test indicates that the alkalizer plays a positive factor for the drug dissolution rate enhancement. The intermolecular interactions in the inclusion complexes were investigated using Fourier transform infrared spectroscopy. It was found that the drug frequency of the C=O band decreased or disappeared when the alkalizer was added. Thermal stability experiments showed that the inclusion complex have better stability after adding alkalizer. The solubility of α-lipoic acid can be increased 40 times when the ratio of α-lipoic acid and sodium carbonate is 1:1.2 in the ternary inclusion complex. It was evident that the inclusion compounds with alkalizer can improved the solubility and stability of α-lipoic acid significantly.