HYDRATION METHOD: A POTENTIAL PROCEDURE FOR BLENDING OLANZAPINE AND CYCLODEXTRINS IN SEMISOLID CONDITION USING A GREEN SOLVENT

Abstract

Olanzapine (OLZ) is an antipsychotic drug with low aqueous solubility. Cyclodextrin (CD) complexation is a potential approach employed to improve the solubility of poorly water-soluble drugs belonging to BCS classes II and IV. The solubility of olanzapine was improved using βCD, HPβCD and methyl βCD which was reported in earlier works. In the current study, a combination of βCD and HPβCD in 1:1 molar ratio was used in the preparation of complexes along with βCD and HPβCD. Methods such as slugging, hydration and granulation which are slight modifications of conventional methods like physical mixing and slugging were used. AL type curves were obtained in phase solubility studies specifying a linear increase in the solubility of drug with increase in concentration of cyclodextrin. The values of slopes calculated for A L type plots are less than one which suggests that OLZ:CD complexes are formed in 1:1 molar ratio. The stability constants obtained were 188.98 M -1, 140.63 M ^-1 and 157.48 M ^-1 with βCD, HPβCD and βCD+HPβCD and these values indicate that stable OLZ : CD complexes are formed. The drug: cyclodextrin binary complexes demonstrated a 2.27 to 3.67 - fold increment in aqueous solubility when compared to pure drug. The percentage of drug released in 60 minutes was 46 (pure drug), 65 - 89 (OLZ-βCD complexes), 59 - 80 (OLZ-HPβCD complexes) and 61 - 84 (OLZ-βCD+HPβCD complexes). Results of DSC, XRD and SEM
indicated partial inclusion complexation. The complexes prepared by hydration method showed higher solubility when compared to other methods. In hydration method, the complexes were prepared using water which does not cause any harm to individual and environment.