持続性塩酸オキシブチニンぼうこう内注入液の製剤化とその評価

Abstract

We developed a prolonged-action oxybutynin hydrochloride (OB) solution (5 mg/10 ml) for intravesical instillation therapy in the treatment of refractory urinary incontinence in neuropathic bladder disease. Hydroxypropylcellulose (HPC) was selected as a viscosifying agent. The OB solution containing HPC (HPC-OB solution) exhibited Newtonian viscosity. Although the release of OB from the HPC-OB solution was retarded by an increase in the HPC concentration, the apparent release rate constant was scarcely affected by solutions with more than a 1.0% HPC. Based on these findings, the optimal concentration of HPC was thus selected to be 1% in pharmaceuticals as a viscosifying agent. The pH of the HPC-OB solution containing 1% HPC was 5.94 and was stable for 6 months under all storage conditions. OB was stable under cold-dark conditions for 6 months. However, the residual content of OB was 94.8 and 95.1% after 6 months storage at room temperature under light and dark conditions, respectively.The urine concentrations of OB after a single intravesical instillation of OB (5 mg/10 ml) were also evaluated. The amount of urine excretion of OB after HPC-OB solution was significantly lower than that after OB solution at first urination. The total amount of urine excretion of OB after HPC-OB solution thus appeared to be low compared with that after OB solution. These results thus suggest that OB may remain intravesically after the instillation of HPC-OB solution for a longer period than that of OB solution.In conclusion, based on the above findings the use of intravesical HPC-OB solution is thus considered to be a more practical procedure than the use of OB solution for controlling incontinence in neuropathic bladder disease.