Flow-through cell dissolution method as predictor of sulfamethoxazole and trimethoprim plasma concentrations: studies using two-dose formulations

The study aimed to predict sulfamethoxazole (SMZ) and trimethoprim (TMP) plasma levels using in vitro release data from the flow-through cell method (USP apparatus IV) and published pharmacokinetic information. Low-dose (400/80 mg) and high-dose (800/160 mg) tablets of both reference and generic fixed-dose combination formulations were tested using USP apparatus IV (22.6 mm cells, laminar flow at 16 ml/min) in a pH 6.8 phosphate buffer. Samples were collected at intervals from 10 to 60 minutes, and the extent of drug dissolution was determined using a spectrophotometric derivative method.Dissolution profiles of generic and reference formulations were compared using the f₂ similarity factor, dissolved drug at the last sampling time, dissolution efficiency, and mean dissolution time (t-test). Additionally, t50%, t63.2%, t85% (from hyperbola models) and Td values (from the Weibull function) were analyzed. While f₂ results indicated similarity (f₂ = 50–100), other comparisons yielded conflicting outcomes. A convolution approach was applied to predict plasma concentrations, and pharmacokinetic parameters such as Cmax and AUC₀-∞ were compared to real pharmacokinetic data. Prediction errors