title: Preparation of olanzapine and methyl-β-cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: An approach to enhance the solubility and dissolution properties.
abstract: The purpose of this study was to evaluate a single-step, organic solvent-free supercritical fluid process for the preparation of olanzapine-methyl-β-cyclodextrin complexes with an express goal to enhance the dissolution properties of olanzapine. The complexes were prepared by supercritical carbon dioxide processing, co-evaporation, freeze drying and physical mixing. The prepared complexes were then analysed by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, solubility and dissolution studies. Computational molecular docking studies were performed to study the formation of molecular inclusion complexation of olanzapine with methyl-β-cyclodextrin. All the binary mixtures of olanzapine with methyl-β-cyclodextrin, except physical mixture, exhibited a faster and greater extent of drug dissolution than the drug alone. Products obtained by the supercritical carbon dioxide processing method exhibited the highest apparent drug dissolution. The characterisation by different analytical techniques suggests complete complexation or amorphisation of olanzapine and methyl-β-cyclodextrin complexes prepared by supercritical carbon dioxide processing method. Therefore, organic solvent-free supercritical carbon dioxide processing method proved to be novel and efficient for the preparation of solid inclusion complexes of olanzapine with methyl-β-cyclodextrin. The preliminary data also suggests that the complexes of olanzapine with methyl-β-cyclodextrin will lead to better therapeutic efficacy due to better solubility and dissolution properties.
authors: Medway Centre for Pharmaceutical Sciences, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, United Kingdom. Electronic address: suman_rudrangijips@yahoo.com.
authors: Shashi Ravi Suman
authors: SR
authors: Rudrangi
authors: Medway Centre for Pharmaceutical Sciences, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, United Kingdom. Electronic address: V.Trivedi@greenwich.ac.uk.
authors: Vivek
authors: V
authors: Trivedi
authors: Medway Centre for Pharmaceutical Sciences, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, United Kingdom.
authors: John C
authors: JC
authors: Mitchell
authors: Medway Centre for Pharmaceutical Sciences, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, United Kingdom.
authors: Stephen Richard
authors: SR
authors: Wicks
authors: Medway Centre for Pharmaceutical Sciences, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, United Kingdom.
authors: Bruce David
authors: BD
authors: Alexander
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002245:Carbon Dioxide / Q000737:chemistry*; D004338:Drug Combinations; D065546:Drug Liberation; D005612:Freeze Drying; D008855:Microscopy, Electron, Scanning; D062105:Molecular Docking Simulation; D000077152:Olanzapine; D012995:Solubility; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D004338:Drug Combinations; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D001569:Benzodiazepines; D002245:Carbon Dioxide; D000077152:Olanzapine
keywords: Freeze drying; Inclusion complexes; Methyl-β-cyclodextrin; Olanzapine; Supercritical carbon dioxide