Stability and compatibility of morphine

Abstract

Morphine is a widely used analgesic for the treatment of severe cancer pain. For a large number of terminally ill patients oral administration is no longer possible and morphine is administered parenterally using portable pumps allowing comfortable treatment of the patient at home. In this situation the storage of pre-filled reservoirs and/or the administration over a longer period of time are daily practices and require data on the stability of morphine solutions. As most of these patients suffer from several other symptoms, the administration of admixtures with other drugs is common and requires information on the compatibility of morphine. Morphine degrades in aqueous solutions with the formation of mainly pseudomorphine, to a lesser extent morphine- N-oxide and probably apomorphine. From the study of the kinetics of morphine degradation it was concluded that the degradation of morphine is accelerated in the presence of oxygen and at higher pH of the solution, whereas temperature and light have only a minor influence on the degradation rate. The data reported on the stability of morphine infusion solutions kept under ambient conditions indicated that oxygen, light, the type of reservoir, the type of diluent, the salt form and the concentration of morphine do not affect the stability of morphine solutions stored for up to 3 months. Morphine solutions should preferably be stored at room temperature in order to avoid precipitation at low temperatures and water evaporation at higher temperatures causing increase in morphine concentration when stored in polymer reservoirs. Analyzing the data available on the compatibility of morphine infusion solutions revealed that differences in the formulation of the drug solutions (drug concentration, salt form, type and concentration of additives) and diluent, as well as temperature and order and ratio of mixing might affect the compatibility. Only few reports provide all necessary information, limiting the information useful for daily practice. Moreover, the majority of the compatibility studies are performed in intensive care units, where other drugs and other concentrations of morphine are required than in palliative care settings, limiting its merit for this sector.