In the present investigation, an attempt has been made to improve aqueous solubility of a
BCS class II drug by making an inclusion complex with Hydroxypropyl-β-cyclodextrin (HP-β-CD).
Paliperidone (PALI) was selected as a model drug for the study. It is practically insoluble in water
with low oral bioavailability. It is a major active metabolite of risperidone approved for the treatment
of schizophrenia in adults. The inclusion complexes were prepared in 1:1 (PALI: HP-β-CD) molar
ratio. Phase solubility studies were performed according to Higuchi Connors method to determine the
optimum conditions for the complexation. The prepared solid inclusion complexes were characterized
by Differential Scanning Calorimetry (DSC), Fourier- Transform Infrared Spectroscopy (FT-IR),
Powder X-ray Diffractometry (PXRD), Scanning Electron Microscopy (SEM) and Proton Nuclear
Magnetic Resonance Spectroscopy (1H-NMR). Dissolution study was performed using USP apparatus
II in phosphate buffer, pH 6.8 (37 ± 0.5oC). The solid state characterization studies confirmed the
formation of inclusion complex between PALI and HP-β-CD. The aqueous solubility and in-vitro
dissolution study showed that the solubility and dissolution rate of drug were considerably improved
by complexation with HP-β-CD with respect to the drug alone. The enhanced solubility and
dissolution may help to improve in-vivo performance of PALI. Thus, the binary complexation of
PALI with HP-β-CD can be used as an approach for its solubility enhancement.
Keywords: Binary complex, cyclodextrin complex, dissolution enhancement, inclusion complex, poorly
soluble, solubility enhancement.
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