App Note: Controlled supersaturation experiments to check the time that additives keep drugs in solution

Controlled Supersaturation experiments provide a way to create supersaturated solutions which can then be monitored to determine the precipitation rate and the time when precipitation starts. This is illustrated using bifonazole, a basic drug with pKa of 6.0.

Experiments with bifonazole

To run the method, a stock solution of sample is prepared in a solvent, e.g. 10 mM in DMSO. An aliquot of stock solution is then injected into an aqueous buffer to create a solution that is supersaturated. This technique is called “solvent-quench”. The transmission of UV at multiple wavelengths is then monitored. While the solution remains supersaturated the UV signal shows constant absorbance values at all wavelengths. As soon as precipitation starts, the absorbance decreases at all wavelengths. Figure 1 shows the behaviour of a supersaturated solution of bifonazole in aqueous buffer at pH 5. After absorbance has been measured, concentration is determined by applying previously-measured molar extinction coefficients…