Studies on solubility enhancement and improvement of oral bioavailability of some bcs class ii drugs

Abstract

newlineThe aim of the present investigation was to prepare cocrystals of a poorly soluble newlineBCS class II drug, Aceclofenac after sceening to enhance its solubility and in turn the newlinebioavailability. newlineThe screening of the cocrystal formers was done by calculating the solubility newlineparameters using Hoftyzer and Van Krevelen solubility parameters and slurry newlinecrystallization technique using seven cocrystal formers. Cocrystals of the drug were newlineprepared using solvent evaporation technique using the selected cocrystal formers i.e. newlineGallic acid and Nicotinamide in the stoichiometric ratio of 1:1. Characterization of the newlineprepared cocrystals was done using Differential Scanning Calorimetry, Fourier newlineTransform Infra red studies, X-Ray Diffraction and Scanning Electron Microscopic newlinetechniques. All the four characterization techniques confirmed the formation of newlinecocrystals of the drug thereby establishing cocrystallization as the method for improving newlinethe physiochemical properties of an active pharmaceutical ingredient. The in vitro newlinedissolution studies of the cocrystals which were formed by solvent evaporation method newlinein the stoichiometric ratio of 1:1 after screening was carried out in pH 1.2 buffer solution newlineusing Shimadzu 1201UV-visible spectrophotometer. The in vivo bioavailability studies newlinewere carried out on adult male New Zealand albino rabbits following a parallel design. newlineThe blood samples were analysed using HPLC. The various pharmacokinetic parameters newlinelike Cmax, Tmax and AUC for the two cocrystals were calculated. Both the cocrystals newlineshowed a better dissolution profile than the pure drug and the physical mixture of the newlinepure drug and the cocrystals former in the in vitro dissolution studies. The oral newlinebioavailability also showed a significant increase of 1.77 and 1.37 times when compared newlineto that of pure Aceclofenac (p lt 0.05).