Enhanced intestinal absorption and bioavailability via proniosomes for bazedoxifene acetate drug

Abstract

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of bazedoxifene acetate by improving solubility, dissolution and intestinal permeability. Methods: Proniosomal powder formulations were prepared with bazedoxifene acetate drug varying the span 60 and cholesterol ratio in the range of 0.8:0.2 to 0.2:0.8 using maltodextrin as carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug: span 60 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies. Results: Physico-chemical studies among various formulations helped in optimization of batch. Good flow properties confirmed from angle of repose values indicate easy filling into capsules. Enhancement in dissolution is due to incorporation of bazedoxifene acetate into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Solid state characterization studies prove the transformation to amorphous form with small particle size improving permeation. No drug excipient interaction was observed and sample is stable in refrigerated conditions. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control. Invivo studies proved enhanced absorption of bazedoxifene acetate drug by oral route. Conclusion: In conclusion, proniosomes provide a powerful and functional way of distribution of inadequately soluble bazedoxifene acetate drug which is proved from in vivo studies based on the enhanced oral delivery.