PHYSICOCHEMICAL CHARACTERIZATION, IN-VITRO STUDIES AND IN-VIVO ASSESSMENT OF DRUG CYCLODEXTRIN INCLUSION COMPLEX FOR ORAL BIOAVAILABILITY ENHANCEMENT OF FEBUXOSTAT

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Abhishek Pathak*, Sadhana J Rajput.
The objective of this research was to enhance the oral bioavailability of Febuxostat (FBX) by preparing the Febuxostat/cyclodextrin inclusion complex. The β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, Methyl-β-cyclodextrin and γ-cyclodextrin were used to prepare inclusion complex with FBX by physical mixing, kneading method and freeze drying method. And 2-hydroxypropyl-β-cyclodextrin was selected as a best fit carrier for inclusion of FBX in (1:1) molar ratio on the basis of phase solubility and inclusion efficiency study. Freeze drying method was found most effective method in terms of solubilization and dissolution of FBX. The physicochemical characterization of prepared inclusion complexes was performed by Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Infra-red spectroscopy (IR) analysis indicated the perfect inclusion of FBX in 2-hydroxypropyl-β-cyclodextrin. Adequate dissolution was achieved in distilled water and phosphate buffer pH-6.8. In-vitro Cell Cytotoxicity Studies (MTT Assay) using Caco-2 cell line model confirmed the bio-tolerability of FBX-inclusion complexes. In vivo assessment demonstrated that freeze dried inclusion complex of FBX with 2-hydroxypropyl-β-cyclodextrin exhibited better pharmacokinetic properties compared to plain FBX and commercial formulation. The relative oral bioavailability of FBX in Albino rabbits resulted from Freeze dried inclusion complex was found 3.08 fold and 2.29 fold greater than plain FBX and marketed formulation, respectively.


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