In vitro prediction of in vivo absorption of ibuprofen from suspensions through rational choice of dissolution conditions

Abstract

Two ibuprofen suspension formulations were investigated for their dissolution in various bicarbonate, phosphate and acetate buffers. Phosphate and acetate gave faster release than bicarbonate at comparable molarities. Nevertheless, mass transport modelling using the reversible non-equilibrium (RNE) approach enabled the calculation of phosphate molarities that gave good matches to physiological bicarbonate in terms of ibuprofen dissolution. This shows that developing surrogate buffers for bicarbonate that are devoid of the technical difficulties associated with the bicarbonate-CO₂ systems is possible. In addition, the intestinal dissolution kinetics of the tested suspensions were determined by applying compartmental pharmacokinetic modelling to plasma profiles that were previously obtained for these suspensions in an in vivo study performed on healthy human volunteers. The in vitro dissolution profiles in bicarbonate compared reasonably well with the profiles representing the in vivo intestinal dissolution kinetics of the tested suspensions when applied to healthy human volunteers in a pharmacokinetic study. This shows the possible potential toward extending biowaivers so that they include BCS class IIa compounds.

Keywords: Bicarbonate; Biowaivers; Buffer; Dissolution; Intestine.