C M Adeyeye1, F F Chen. 1. Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282, USA. adeyeyechri@duq3.cc.duq.edu
Abstract
PURPOSE: The aim of the study is to evaluate stereoselective in vivo disposition of suspensions of conventional and wax-matrix sustained release ibuprofen microspheres in rats. METHODS: Male wistar rats were dosed i.v. with 20 mg/kg, or orally with conventional suspension, and three suspension formulations of sustained release microspheres (having three different particle sizes) of racemic ibuprofen. Blood samples were analyzed stereoselectively by reverse phase HPLC. RESULTS: The mean Cmax for (S)- and (R)-ibuprofen decreased with increased particle size of the drug or microspheres in the suspension dosage forms, while the Tmax increased with increased particle size. The mean S/R ratio (AUC0-48) of the suspensions decreased with increase in particle size of the drug or microspheres and these ratios (for both conventional and sustained formulations) were higher than that of the i.v., an indication of presystemic inversion. Decrease in the ratios with increased particle size is suggestive of formulation dependent inversion. The plasma concentration-time data of the sustained release formulations showed bimodal profiles, irrespective of the particle size of the microspheres. The second peak observed after 8 hours is indicative of colonic absorption. CONCLUSIONS: Stereoselective disposition of ibuprofen microspheres showed higher bioavailability compared to the conventional suspension. Bimodal disposition is influenced by dosage form while presystemic inversion is both site-specific, and dosage form dependent.
PURPOSE: The aim of the study is to evaluate stereoselective in vivo disposition of suspensions of conventional and wax-matrix sustained release ibuprofen microspheres in rats. METHODS: Male wistar rats were dosed i.v. with 20 mg/kg, or orally with conventional suspension, and three suspension formulations of sustained release microspheres (having three different particle sizes) of racemic ibuprofen. Blood samples were analyzed stereoselectively by reverse phase HPLC. RESULTS: The mean Cmax for (S)- and(R)-ibuprofen decreased with increased particle size of the drug or microspheres in the suspension dosage forms, while the Tmax increased with increased particle size. The mean S/R ratio (AUC0-48) of the suspensions decreased with increase in particle size of the drug or microspheres and these ratios (for both conventional and sustained formulations) were higher than that of the i.v., an indication of presystemic inversion. Decrease in the ratios with increased particle size is suggestive of formulation dependent inversion. The plasma concentration-time data of the sustained release formulations showed bimodal profiles, irrespective of the particle size of the microspheres. The second peak observed after 8 hours is indicative of colonic absorption. CONCLUSIONS: Stereoselective disposition of ibuprofen microspheres showed higher bioavailability compared to the conventional suspension. Bimodal disposition is influenced by dosage form while presystemic inversion is both site-specific, and dosage form dependent.