Physicochemical stability of ready-to-administer mitomycin C solutions for intravesical instillation.

Abstract

Objective: The aim of the study was to investigate the physicochemical stability of mitomycin-containing medicinal products for bladder instillation, formulated with urea as excipient (mito-medac®, Mitomycin medac). For comparison, the stability of reconstituted Urocin® and Mitem® bladder instillation was studied.

Methods: Mitomycin-containing medicinal products were either reconstituted with the prepackaged 0.9% NaCl solution, nominal volume 20 mL (mito-medac®, Mitem®, Urocin®) or with 20 mL water for injection (Mitomycin medac, Mitem®, Urocin®) to a nominal concentration of 1 mg/mL and stored at room temperature (20-25°C). Samples were taken immediately after reconstitution and after 24 hours. Physicochemical stability was determined by reverse-phase high performance liquid chromatography with photodiode array detection, measurement of pH and osmolarity, and inspection for visible particles or colour changes.

Results: The initial pH values of the test solutions reconstituted with prepackaged 0.9% NaCl (5.2-5.6) were significantly lower than those reconstituted with water for injection (6.6-7.4). Solutions reconstituted with 0.9% NaCl solutions rapidly degraded and concentrations fell below the 90% limit after 24 hours of storage. When reconstituted with water for injection, degradation was less rapid. Concentrations of Mitomycin medac and Urocin remained above the 90% limit after 24 hours.

Conclusions: The physicochemical stability of mitomycin 1 mg/mL bladder instillation prepared with prepackaged 0.9% NaCl in prefilled PVC bags is less than 24 hours at room temperature. Unfavourable pH values of the solvents cause rapid degradation of mitomycin. Mitomycin solutions reconstituted at the point of care should be administered immediately to avoid degradation and loss of efficacy. Urea added as excipient did not accelerate degradation.