Solubilization and Stability of Mitomycin C Solutions Prepared for Intravesical Administration

Background: Mitomycin C (MMC) is an antitumor agent that is often administered intravesically to treat bladder Cancer. Pharmacologically optimized studies have suggested varying methods to optimize delivery, with drug concentration and solution volume being the main drivers. However, these MMC concentrations (e.g. 2.0 mg/mL) supersede its solubility threshold, raising major concerns of inferior drug delivery.

Objective: In this study, we seek to confirm that the pharmacologically optimized MMC concentrations are achievable in clinical practice through careful modifications of the solution preparation methods.

Methods: MMC admixtures (1.0 and 2.0 mg/mL) were prepared in normal saline using conventional and alternative compounding methods. Conventional methodology resulted in poorly soluble solutions, with many visible particulates and crystallates. However, special compounding methods, which included incubation of solutions at 50 °C for 50 min followed by storage at 37 °C, were sufficient to solubilize drug. Chemical degradation of MMC solutions was determined over 6 h using high-performance liquid chromatography (HPLC) analytics, while physical stability was tested in parallel.

Results: Immediately following the 50 min incubation, both MMC solutions exhibited approximately 5-7% drug degradation. Based on the measured concentrations and linear regression of degradation plots, additional storage of these solutions at 37 °C for 5 h retained chemical stability criterion (< 10% overall drug loss). No physical changes were observed in any solutions at any test time points.

Conclusion: We recommend that the described alternative preparation methods may improve intravesicular delivery of MMC in this urological setting, and advise that clinicians employing these changes should closely monitor patients for MMC toxicities and pharmacodynamics (change in clinical outcomes) that result from the potential enhancement of MMC exposure in the bladder.