SOLUBILITY ENHANCEMENT OF BCS CLASS II DRUG USING LYOPHILISATION TECHNIQUE AND DETERMINATION OF BIOAVAILABILITY IN ANIMALS USING CATALEPSY MODEL

摘要

Ziprasidone HCl is a newly introduced atypical antipsychotic drug. It has its own unique multi receptor binding affinity. This makes it a unique special choice of antipsychotic agent. It mainly acts as antagonist of D₂ dopamine receptors as and 5HT₂A (serotonin, 5HT, 5-hydroxytryptamine) receptors. It is pinkish brown colored powder having very low solubility in water (21.12 mg/L). The main purpose of this study is to enhance the solubility of Ziprasidone HCl using lyophilisation technique. The β-Cyclodextrine and Hydroxy Propyl- β-Cyclodextrine were used as the water soluble carriers for increasing the solubility of Ziprasidone. All the inclusion complexes prepared by lyophilisation technique showed remarkable increase in the solubility compared to the pure Ziprasidone HCl. The saturation solubility analysis demonstrated highest increase in the solubility of drug after complexation with HP-β-CD by lyophilisation technique. The inclusion complexes were characterized using DSC and XRD technique. During in vitro study result obtained that the lyophilized complexes with HPβ-CD showed 100% drug release within 10 min were as the lyophilized complexes with β– CD showed 100% drug release in 25 min. Therefore the freeze dried complex with HP-β-CD was selected for Catalepsy study on Wistar rats. In the catalepsy study the selected inclusion complex showed increase in bioavailability compared to the drug and almost all the data obtained from study was found to be 99.99% significant with the control.