Physical and Chemical Stability of Morphine Sulfate 5mg/mL and 50mg/mL Packaged in Plastic Syringes

The objective of this study was to evaluate the physical and chemical stability of morphine sulfate in concentrations of 5 mg/mL in 0.9% sodium chloride injection and 50 mg/mL in both 0.9% sodium chloride injection and in sterile water for injection packaged in plastic syringes. Test samples of morphine sulfate 5-mg/mL and 50-mg/mL solutions were packaged as 20 mL of drug solution in 30-mL plastic syringes, sealed with plastic tip caps, and stored at 4 deg C and 23 deg C for 60 days. Test samples were also stored at -20 deg C and 37 deg C (temperature extremes that might be encountered during shipping) for 2 days. Evaluations of physical and chemical stability were performed initially and throughout the storage periods. Physical stability was assessed by means of visual observation in normal room light as well as with a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stabililty of the drug was evaluated by using a stability-indicating high-performance liquid chromatographic (HPLC) analytical technique. All samples of morphine sulfate 5-mg/mL solutions stored at 4 deg C, 23 deg C, and 37 deg C and the 50-mg/mL solutions stored at 23 deg C and 37 deg C remained free of precipitation throughout the study. In those solutions, little or no change in measured particulate burden or haze level was found, However, the solutions of morphine sulfate 50 mg/mL in 0.9% sodium chloride injection and in sterile water for injection exhibited an obvious precipitate within 2 to 4 days of storage at 4 deg C. Warming the solution to redissolve the visible precipitate left a substantial microparticulate content of up to 29,000 microparticulates/mL. When both morphine sulfate concentrations were frozen, precipitation was also noted. Upon thawing, the solutions yielded substantial measured microparticulate quantities of more than 20,000 microparticulates/mL in the 5-mg/mL concentration and more than 52,000 microparticulates/mL in the 50 mg/mL concentration. In addition, morphine sulfate 50mg/mL in both diluents exhibited a slight yellow discoloration after 30 days of storage at 23 deg C. Little or no loss of morphine sulfate occurred in any of the samples at any storage temperature throughout the study. Analysis of the samples after redissolving the visible precipitate in the low-temperature samples demonstrated that the morphine sulfate remained intact. Morphine concentrations were found to be 95% or greater over 60 days when stored at both 4 deg C and 23 deg C. In addition, morphine concentrations were greater than 97% when stored at -20 deg C, and they were 98% or greater when stored at 37 deg C after 2 days. However. exposure to low temperatures may result in precipitation, including microparticulate content that does not fully redissolve upon warming.