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

The formation steps of inclusion complex caused by co-grinding loratadine (LOR) and hydroxypropyl-β-cyclodextrin (HP-β-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-β-CD were also examined. The result indicates that the aqueous solubility of LOR was linearly increased with the increase of HP-β-CD concentrations, in which the phase solubility diagram was classified as AL type. The higher apparent stability constant (2.22 × 104 M−1) reveals that the inclusion complex formed between LOR and HP-β-CD was quite stable. The endothermic peak at 134.6 °C for the melting point of LOR gradually disappeared from DSC curves of LOR/HP-β-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-β-CD coground mixture or the co-evaporated solid products was due to the inclusion complex formation between LOR and HP-β-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-β-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-β-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-β-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.