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Abstract:  The objective of this study was to evaluate the physical and chemical stability of morphine sulfate 5 mg/mL with bupivacaine hydrochloride 2.5 mg/mL in 0.9% sodium chloride injection and morphine sulfate 50 mg/mL with bupivacaine hydrochloride 25 mg/mL in sterile water for injection packaged in plastic syringes.

Test samples of morphine sulfate 5-mg/mL with bupivacaine hydrochloride 2.5-mg/mL and morphine sulfate 50-mg/mL with bupivacaine hydrochloride 25-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°C and 23°C for 60 days. Test samples were also stored at -20°C and 37°C (temperature extremes that might be encountered during shipping) for 2 days. Evaluations for physical and chemical stability were performed initially and throughout the storage periods. Physical stability was assessed by means of visual observation under normal room light and with a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the drug was evaluated with a stability-indicating high-performance liquid chromatographic (HPLC) analytical technique.

All test samples remained free of visible precipitation throughout the study. The inclusion of the bupivacaine hydrochloride prevented the precipitation of morphine sulfate that occurs at a lower storage temperature. For solutions stored at 4°C, 23°C, and 37°C, little or no change in measured particulate burden and haze level were found. However, samples stored frozen at -20°C exhibited a substantial microparticulate content upon thawing that was measured to be nearly 12,000 microparticulates/ mL. Most samples were clear and colorless throughout the study. However, morphine sulfate 50 mg/mL with bupivacaine hydrochloride 25 mg/mL exhibited a slight yellow discoloration after 7 days of storage at 23°C.

Little or no loss of morphine sulfate and bupivacaine hydrochloride occurred in any of the samples at any storage temperature throughout the study. Morphine concentrations were found to be about 97% or greater, and bupivacaine hydrochloride concentrations were about 95% or greater throughout the study period under each storage condition. Morphine sulfate solutions at concentrations ranging from 5 mg/mL to 50 mg/mL combined with bupivacaine hydrochloride 2.5 mg/mL to 25 mg/mL can be packaged in plastic syringes, stored, and shipped with little or no loss of drug. However, freezing should be avoided.

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Related Categories: PEER-REVIEWED, STABILITIES, COMPATIBILITIES

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