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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

Rudrangi, S R S, Trivedi, Vivek, Mitchell, John C., Wicks, Stephen, Alexander, Bruce D. (2015) 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. International Journal of Pharmaceutics, 494 . pp. 408-416. ISSN 0378-5173. (doi:10.1016/j.ijpharm.2015.08.062) (KAR id:73631)

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.

Item Type: Article
DOI/Identification number: 10.1016/j.ijpharm.2015.08.062
Uncontrolled keywords: Olanzapine, Methyl-β-cyclodextrin, Inclusion complexes, Freeze drying, Supercritical carbon dioxide
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Central Services > Universities at Medway
Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Vivek Trivedi
Date Deposited: 25 Apr 2019 12:21 UTC
Last Modified: 16 Feb 2021 14:04 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/73631 (The current URI for this page, for reference purposes)

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