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Published on: August 15, 2016
Formulation and characterization of amiodarone-methyl-beta-cyclodextrin inclusion complexes: A molecular modelling
Alexandre M Rubim1, Jaqueline B Rubenick2, Laura O Vendrame3
1Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria - UFSM, Av. Roraima 1000, 97105-900, Santa Maria, RS, Brazil; Laboratório de Controle de Qualidade de Medicamentos, Universidade Franciscana - UFN, Andradas 1614, 97010-032, Santa Maria, RS, Brazil.
Abstract:
This study aimed to develop immediate-release tablets containing amiodarone hydrochloride (AM). AM is a BCS class II compound, i.e., high permeable, and poorly soluble. The interactions between amiodarone and methyl-β-cyclodextrin were DFT-based, theoretically measured, supporting the complexation of AM with cyclodextrin by using methyl-β-cyclodextrin through a spray-drying process. Thus, increasing substantially the drug solubility to 93.31% and 87.14%, respectively. Solubility studies demonstrated the formation of the Drug-Methyl-β-cyclodextrin inclusion complex with 1:1 stoichiometry. The complex formation was characterized by SBET, XRD, DSC, SEM, FTIR, and 1H NMR. Complementing, immediate-release tablets containing the inclusion complex were developed by direct compression, and in vitro dissolution studies were performed in gastrointestinal fluids using USP Pharmacopeia standard dissolution rate testing equipment. The dissolution rate of immediate-release tablets was substantially higher than the pristine drug in all mediums evaluated. These results confirm the application of methyl-β-cyclodextrin as an effective excipient for incorporation in novel dosage forms to increase the solubility of poorly soluble drugs.
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