Een pilotstudie naar de farmaceutische formulering, stabiliteit en af gif teprofiel van een intraperitoneaal toe te dienen hydrogeloplossing met irinotecan

Background Peritoneal metastases are commonly treated by cyto-reductive surgery followed by hyperthermic intraperitoneal chemotherapy. However, survival outcomes remain poor and better treatment options with more effective local drug exposure are warranted. A potential alternative could be an intraperitoneally administered hydrogel solution as carrier for chemotherapy, allowing a slow and controlled drug release from the gel. In this pilot study, we assessed the formulation, stability and in vitro drug release of irinotecan from a biologically resorbable polymer hydrogel solution. Objective Define the requirements for a hydrogel solution and explore how this hydrogel solution could be formulated to obtain a stable product that is suitable for use in clinical trials and releases irinotecan over multiple days. Design and methods In a qualitative research physicians and pharmacists were interviewed to identify the desired clinical use, formulation and compounding of the polymer hydrogel solution. Outcomes of this study were investigated in an explorative research. The polymer concentration, sterilization temperature, primary package and in vitro release profile were investigated, and stability tests were conducted. Results A polymer concentration of 6% resulted in adequate gel forming capacity, whereas this was absent at a concentration of 4%. In vitro, irinotecan was constantly released from a hydrogel solution of 6% during the first 24 hours. High temperatures (116 °C) caused degradation of the polymer, less degradation occurred at 110 °C. Storage in a plastic syringe without air did not negatively affect stability of the hydrogel, however, storage in glass with air resulted in increased viscosity. Conclusion This pilot study showed that a stable hydrogel solution of 6% in a plastic syringe can be obtained that is capable of releasing irinotecan over 24 hours. The optimal sterilisation temperature and concentration range has not been established yet. Additional research is needed, before definite conclusions can be drawn.