Stability of morphine sulfate in polypropylene infusion bags for use in patient-controlled analgesia pumps for postoperative pain management.

The objective of this study was to develop a stable intravenous solution of 1-mg/mL morphine sulfate in polypropylene bags for use in patient-controlled analgesia pumps for postoperative pain management. Three large-scale batches of 1-mg/mL morphine sulfate solution filled into polypropylene bags and terminally sterilized at 120 deg C for 20 minutes were used in this study. The stability of the drug was monitored at 3, 6, 12, 18, 24, and 36 months after preparation in a long-term study (25 deg C) and after 3 and 6 months in accelerated studies (30 and 40 deg C) using a stability-indicating high-performance liquid chromatography assay. The levels of degradation products (morphine-N-oxide and pseudomorphine) were determined. Measures of physical stability included pH values, presence of subvisible particles, and weight loss. Microbiological stability was tested by performing sterility test. There was practically no loss of morphine, and impurity contents were very low. Subvisible particles were below pharmacopeial specifications. No significant change in pH was observed and water losses were minimal. The sterility of the bags was demonstrated throughout the study. In conclusion, terminally sterilized 1-mg/mL morphine sulfate solution packed in polypropylene bags is stable for at least 3 years when stored at 25 deg C.