Compatibility and stability of bryostatin 1 in infusion devices

Bryostatin I is currently in phase II clinical trial sponsored by the Natio nal Cancer Institute as an anticancer chemotherapeutic agent. Bryostatin 1 for injection was supplied in a dual pack containing a drug vial and a dilu ent vial and was manufactured by Ben Venue Laboratories, Inc (Bedford, OH). The stability and compatibility of the bryostatin 1-PET formulation, dilut ed to 1 and 10 mu g/mL in saline and benzyl alcohol preserved saline, with polypropylene(PP) and polyvinyl chloride (PVC) bags at room temperature (27 degrees C) were studied. All experiments were conducted in triplicate and analyses were performed using a validated, stability-indicating, high perfo rmance liquid chromatography (HPLC) assay. Bryostatin 1 solutions were compatible with PP bags. At both concentrations and with both salines, the bryostatin content remained unchanged during th e 28-day storage period, benzyl alcohol concentration in the preserved sali ne solutions also remained relatively constant. In PVC bags, however, a dec rease in bryostatin 1 concentrations without generation of decomposition pr oducts was observed at both dilutions and with both salines during the 28-d ay storage. A decrease in benzyl alcohol concentration in the preserved sal ine was also observed. While no diethylhexylphthalate (DEHP) leakage into t he solution was observed in PP bags, DEHP leakage in PVC infusion bags was observed on day 2 of storage which increased with storage time and leveled off on day 6. The amount of DEHP leached into drug solution is dependent on the drug concentration. This study suggests bryostatin-PET formulation dil uted with preserved saline can be used for long-term (4 week) intravenous a dministration using PP infusion bags, but not with PVC bags.