Sadhana J Rajput

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.

Two simple, rapid, precise and accurate spectrophotometric methods have been developed for simultaneous analysis of Ibuprofen (IBU) and Famotidine (FAMO) in their combined dosage form. Method A, absorbance correction method involves measurement of amplitudes at 220 nm (for IBU) and 288 nm (for FAMO) in zero derivative spectra. Method B, ratio derivative spectrophotometry, involves division of spectra of IBU by one selected standard spectrum of FAMO and then measuring amplitudes at 234.2 nm in ratio derivative spectra for estimation of IBU. Similarly, spectra of FAMO are divided by one selected standard spectrum of IBU and then amplitudes at 277.8 nm in ratio derivative spectra are measured for estimation of FAMO. Developed methods were validated according to ICH guidelines. The calibration graph follows Beer’s law in the range of 2 to 60 µg/ml for IBU and 3.8 to 4.6 µg/ml for FAMO with R2 value greater than 0.999. Accuracy of all methods was determined by recovery studies and showed % recovery between 98 to 102%. Intraday and Interday precision was checked for both the methods and mean %RSD was found to be less than 2 for these methods. The methods were successfully applied for estimation of IBU and FAMO in marketed formulation.