Ternary Inclusion Complex of Paliperidone with β-Cyclodextrin and Hydrophilic Polymer for Solubility and Dissolution Enhancement

Abstract

The present study was aimed to improve aqueous solubility and dissolution behavior of a poorly water-soluble antipsychotic drug, Paliperidone (PLDN), through the formation of inclusion complexes with beta-cyclodextrin (β-CD). The effect of water soluble polymer on the complexation efficiency and solubilizing ability of β-CD was investigated using Kollidon-30 (KDN) as a ternary component. The binary complex of PLDN: β-CD was prepared by co-precipitation method in 1:1 molar ratio and ternary complex was prepared analogously to the binary complex containing 0.3% of KDN. The solid state characterization of the complexes was carried out using DSC, FTIR, XRPD, and SEM studies. The phase solubility study carried out according to the Higuchi and Connors method revealed an increase in complexation efficiency of β-CD due to addition of KDN. Saturation solubility and in vitro dissolution studies of complexes showed that the aqueous solubility and dissolution rate of drug were improved substantially compared to drug alone. The ternary complex resulted more solubility enhancement and drug release compared to binary complexes. In conclusion, the addition of KDN to the binary system of PLDN:β-CD has a synergistic effect on the solubility enhancement ability of β-CD. Hence, ternary complexation can be used as a novel approach for solubility enhancement of PLDN.