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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 clonidine hydrochloride 0.25 mg/mL in 0.9% sodium chloride injection and morphine sulfate 50 mg/mL with clonidine hydrochloride 4 mg/mL in sterile water for injection when packaged in plastic syringes.

Test samples of morphine sulfate 5-mg/mL with clonidine hydrochloride 0.25-mg/mL and morphine sulfate 50-mg/mL with clonidine hydrochloride 4-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 in 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 by means of a stability-indicating high-performance liquid chromatographic (HPLC) analytical technique.

All samples of morphine sulfate 5-mg/mL with clonidine hydrochloride 0.25-mg/mL solutions stored at 4°C, 23°C, and 37°C and the morphine sulfate 50-mg/mL with clonidine HCl 4-mg/mL solutions stored at 23°C and 37°C remained free of precipitation throughout the study. Little or no change in measured particulate burden and haze level were found in those solutions. However, morphine sulfate 50 mg/mL with clonidine HCl 4 mg/mL stored at 4°C exhibited an obvious precipitate within 2 to 4 days. Warming the solution to redissolve the precipitate left a substantial microparticulate content that was measured to be more than 33,000 microparticulates/mL. Upon freezing, both high- and low-concentration samples precipitated and yielded substantial measured microparticulate quantities up to 35,000 microparticulates/mL in the low-concentration combination and 50,000 microparticulates/mL in the high-concentration combination. In addition, as with morphine sulfate 50 mg/mL alone, the high-concentration combination exhibited a slight yellow discoloration after 30 days of storage at 23°C.

Little or no loss of morphine sulfate and clonidine hydrochloride occurred in any of the samples at any storage temperature throughout the study. Morphine concentrations were found to be about 98% or greater, and clonidine hydrochloride concentrations were about 97% or greater throughout the study period under each storage condition. Morphine sulfate solutions at concentrations ranging from 5 to 50 mg/mL combined with clonidine hydrochloride ranging from 0.25 to 4 mg/mL can be packaged in plastic syringes, Physical and Chemical Stability of Low and High Concentrations of Morphine Sulfate with Clonidine Hydrochloride 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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