The effect of buffer species on biorelevant dissolution and precipitation assays - Comparison of phosphate and bicarbonate buffer.

Biorelevant solubility and dissolution testing is an important tool during pharmaceutical development, however, solubility experiments performed using biorelevant media often do not properly match the solubility data observed in human intestinal fluids. Even though the bicarbonate buffer is the predominant buffer system in the small intestine, in vitro assays are commonly performed using non-volatile buffer systems like phosphate and maleate. In the current study, bicarbonate- and phosphate-buffered biorelevant media were applied to solubility, dissolution, and precipitation testing for a broad range of model compounds. It was found that the medium affects primarily the dissolution kinetics. However, with the knowledge of the unique buffering properties of bicarbonate buffer in the diffusion layer, it was not always possible to predict the effect of buffer species on solubility and dissolution when changing from phosphate to bicarbonate buffer. This once again highlights the special role of bicarbonate buffer for simulating the conditions in the human intestinal fluids. Moreover, it is necessary to further investigate the factors which may cause the differences in solubility and dissolution behavior when using phosphate- vs. bicarbonate-buffered biorelevant media.