Conditions causing gemcitabine crystallization

Introduction. Intravesical delivery of chemotherapy agents is used very commonly for the treatment of superficial bladder cancer. We recently completed a phase II study of intravesical gemcitabine in which an alkaline adjusted gemcitabine preparation was used initially, based on very early phase I studies. However, crystallization was noted in some of the pre-prepared syringes, which prompted us to investigate the conditions under which gemcitabine crystallized.Methods. Gemcitabine was prepared in syringes in triplicate and conditions were varied with respect to pH, temperature, and duration. Samples were observed for up to 48h for the development of crystallization. High-performance liquid chromatography analysis of gemcitabine concentrations was undertaken for all samples.Results. Crystallization of gemcitabine was favored under conditions of bicarbonate treatment and lowering of temperature. However, the process was reversible, as demonstrated by recovery of gemcitabine concentrations in samples brought back to room temperature. Crystallization resulted in reduction of gemcitabine concentrations in the pre-prepared syringes.Conclusions. Gemcitabine solutions may be associated with crystallization if the native pH is increased with the addition of sodium bicarbonate, and samples are stored in a cold environment.