LAUSR

Purpose The design of biorelevant conditions for in vitro evaluation of orally administered drug products is contingent on obtaining accurate values for physiologically relevant parameters such as pH, buffer capacity and bile salt concentrations in upper gastrointestinal fluids. Methods The impact of sample handling on the measurement of pH and buffer capacity of aspirates from the upper gastrointestinal tract was evaluated, with a focus on centrifugation and freeze-thaw cycling as factors that can influence results. Since bicarbonate is a key buffer system in the fasted state and is used to represent conditions in the upper intestine in vitro , variations on sample handling were also investigated for bicarbonate-based buffers prepared in the laboratory. Results Centrifugation and freezing significantly increase pH and decrease buffer capacity in samples obtained by aspiration from the upper gastrointestinal tract in the fasted state and in bicarbonate buffers prepared in vitro . Comparison of data suggested that the buffer system in the small intestine does not derive exclusively from bicarbonates. Conclusions Measurement of both pH and buffer capacity immediately after aspiration are strongly recommended as “best practice” and should be adopted as the standard procedure for measuring pH and buffer capacity in aspirates from the gastrointestinal tract. Only data obtained in this way provide a valid basis for setting the physiological parameters in physiologically based pharmacokinetic models.