Convolution approach to estimate the in vivo behavior of ibuprofen soft gelatin capsules from in vitro release data of USP Apparatus 4

Abstract

Hypothetical plasma concentration-time profiles of ibuprofen gelatin soft capsules were calculated using data from the USP apparatus IV (flow-through cell method). Four ibuprofen formulations (reference and generic products at 400 and 600 mg) were tested with laminar flow at 16 ml/min in pH 6.8 phosphate buffer. Samples were withdrawn at 10, 20, 30, 45, and 60 minutes, and dissolved drug levels were measured using UV derivative spectrophotometric analysis. Dissolution curves were compared by calculating model-dependent and model-independent parameters, employing Student’s t-test for statistical analysis (significance set at p < 0.05). The dissolution data were fitted to various mathematical models to explain ibuprofen's in vitro dissolution. Hypothetical plasma concentration-time profiles were also calculated using published pharmacokinetic data from in vivo studies combined with a convolution approach. Validation of results was assessed using prediction error (PE) data for two key pharmacokinetic parameters: peak plasma concentration (Cmax) and area under the curve from zero to infinity (AUC0-inf), with validity determined by a PE of ≤ 10%. Similar dissolution profiles were identified for the 400 mg formulations (f2 similarity factor), while dissimilarities were noted in other comparisons (f2 < 50, p < 0.05). The Weibull function best described the dissolution rate of the tested formulations. For the 400 mg reference product, PE values for Cmax and AUC0-inf were < 10%. A discriminatory dissolution method is essential for the 600 mg products, and further in vivo testing is necessary to corroborate the findings.