Inclusion of Diacerein with cyclodextrin carriers: Preparation, physicochemical characterization, cytotoxicity assessment and pharmacological evaluation

摘要

ABSTRACT The present investigation aims on the preparation and in-vitro/in-vivo examination of inclusion complex of Diacerein (DAR) an anthraquinone derivative indicated for treatment of osteoarthritis by inhibiting interlukin-1 and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, the inclusion complexes of DAR with β-cyclodextrin (β-CD), HP-β-CD, methyl-β-cyclodextrin (M-β-CD) and γ-cyclodextrin (γ-CD) were prepared and characterized for phase solubility study and inclusion efficiency. On the basis of results obtained, HP-β-CD was selected to prepare inclusion complexes with DAR by physical mixing, kneading method and freeze drying method and subjected to solid state characterizations. Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Infra-red spectroscopy (IR) analysis confirmed the formation of perfect inclusion complex of DAR with HP-β-CD in solids. In-vitro dissolution and % drug content of DAR in freeze dried inclusion complex showed its superiority over plain drug and commercial formulation. . In-vitro cell cytotoxicity studies (MTT Assay) using Caco-2 cell line model confirmed the bio-tolerability of DAR-inclusion complex. . The relative oral bioavailability of DAR in Albino rabbits resulted from Freeze dried inclusion complex was found 3.32 fold and 2.03 fold greater than plain DAR and marketed formulation, respectively which ultimately demonstrated the enhancement of oral bioavailability of DAR in freeze dried inclusion complex with HP-β-CD. Keywords: Inclusion complex, Diacerein, cyclodextrin, cytotoxicity, bioavailability