How to stop disproportionation of a hydrochloride salt of a very weakly basic compound in a non-clinical suspension formulation

Our objectives were to stabilize a non-clinical suspension for use in toxicological studies and develop methods investigate the stability of formulation terms salt disproportionation. The compound under research was hydrochloride practically insoluble discovery ODM-203. first three approaches prepared stored at room temperature. second stabilized by pH adjustment. In third approach cooling used prevent 5 mg/mL aqueous consisting 20 PVP/VA Tween 80 each approaches. polymer as precipitation inhibitor provide prolonged supersaturation while enhance dissolution homogeneity suspension. consequences disproportionation studied small-scale vitro method an vivo pharmacokinetic study rats. results show that successfully suppressed applying ice bath 2–8 °C. This procedure enabled us proceed obtained showed adequate exposures with acceptable variation dose level.