Salicylic Acid/γ-Cydodextrin 2:1 and 4:1 Complex Formation by Sealed-Heating Method

A novel complex of salicylic acid (SA) and γ-cyclodextrin (γ-CD) was obtained via the sealed-heating method. The influence of the water content of γ-CD on the complex formation with SA by sealed-heating process was investigated. Quantitative determination of SA revealed that sealed-heated samples of SA and γ-CD with low water content (0.8-5.4%) formed the SA/γ-CD = 2:1 complex, while the samples with high water content (8.5-11.5%) formed the SA/γ-CD = 4:1 complex. The molecular arrangements of γ-CD in 2:1 and 4:1 complexes were determined by powder X-ray diffraction measurements to be in monoclinic-columnar and tetragonal- columnar forms, respectively. The results of infrared spectroscopy and 13C solid-state NMR measurements showed that two types of SA molecules resided in the 4:1 complex, whereas only one type of SA molecules existed in the 2:1 complex. The obtained 2:1 complex was assumed to contain two SA molecules per one γ-CD, with the SA molecules existing in the intermolecular spaces formed by the γ-CD columns. In the case of the 4:1 complex, two SA molecules were incorporated into the intermolecular spaces while the other two SA molecules were included within the γ-CD cavity. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4192-4200, 2010