Curve-fitting FTIR studies of loratadine/hydroxypropyl-β-cyclodextrin inclusion complex induced by co-grinding process

Abstract

The formation steps of inclusion complex caused by co-grinding loratadine (LOR) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with a molar ratio of 1:1 or 1:2 were quantitatively investigated by Fourier transform infrared (FTIR) spectroscopy with curve-fitting analysis and differential scanning calorimetry (DSC). The phase solubility study and the co-evaporated solid products of the mixture of LOR and HP-beta-CD were also examined. The result indicates that the aqueous solubility of LOR was linearly increased with the increase of HP-beta-CD concentrations, in which the phase solubility diagram was classified as A(L) type. The higher apparent stability constant (2.22 x 10(4)M(-1)) reveals that the inclusion complex formed between LOR and HP-beta-CD was quite stable. The endothermic peak at 134.6 degrees C for the melting point of LOR gradually disappeared from DSC curves of LOR/HP-beta-CD coground mixtures by increasing the cogrinding time, as the disappearance of the co-evaporated solid products. The disappearance of this endothermic peak from LOR/HP-beta-CD coground mixture or the co-evaporated solid products was due to the inclusion complex formation between LOR and HP-beta-CD after cogrinding process or evaporation. Moreover, IR peaks at 1676 cm(-1) down-shifted from 1703 cm(-1) (CO stretching) and at 1235 cm(-1) upper-shifted from 1227 cm(-1) (C-O stretching) related to LOR in the inclusion complex were observed with the increase of cogrinding time, but the peak at 1646 cm(-1) due to O-H stretching of HP-beta-CD was shifted to 1640 cm(-1). The IR spectrum of 15 min-coground mixture was the same as the IR spectrum of the co-evaporated solid product, strongly indicating that the grinding process could cause the inclusion complex formation between LOR and HP-beta-CD. Three components (1700, 1676, and 1640 cm(-1)) and their compositions were certainly obtained in the 1740-1600 cm(-1) region of FTIR spectra for the LOR/HP-beta-CD coground mixture and the co-evaporated solid products by curve-fitting analysis. The component of 1700 cm(-1) detected was due to the un-included LOR in the inclusion complex. This implies that FTIR spectroscopy with curve-fitting analysis might be useful for discriminating the components and compositions in the inclusion complex.