Factors affecting the physical and chemical stability of morphine sulphate solutions stored in syringes

Abstract

Abstract The stability of morphine sulphate solution (2mg/ml in 0.9 per cent w/v saline) was determined after storage in two brands and two sizes of polypropylene syringes, with or without 0.1 per cent w/v sodium metabisulphite. The suitability of plastic syringes for the long term storage of morphine solutions was further investigated by an assessment of sorption onto or into the syringe, vapour loss and oxygen permeability. A comparison was also made with storage in glass syringes. Measurement of morphine sulphate was by a stability-indicating high performance liquid chromatographic assay. After six weeks, a small loss (<5 per cent) in potency was detected due to oxidation in polypropylene syringes without antioxidant. Polypropylene syringes showed little resistance to oxygen permeation. Oxidation was greater in glass syringes compared with polypropylene syringes, possibly due to release of caustic material. Although inclusion of sodium metabisulphite 0.1 per cent w/v offered protection against oxidation, and the breakdown product pseudomorphine was not detected, the antioxidant was incompatible with morphine under these conditions, resulting in the formation of an unknown substance or complex. To summarise, an acceptable level of stability was observed after storage of morphine solutions in 30ml or 50ml three-piece polypropylene syringes in the dark, at room temperature, for six weeks. While such syringes are not protected from oxygen permeation and are susceptible to oxidation over the longer term, all attempts at using glass syringes or an antioxidant were unsuccessful due to a number of factors.