The stability of morphine in isobaric and hyperbaric solutions in a drug delivery system

Abstract

Intrathecal preparations of morphine for use in intractable pain must contain no preservatives. They are generally formulated in saline (isobaric) or dextrose (hyperbaric) which raises questions of stability. The behaviour of morphine in hyperbaric and isobaric solutions stored in a reservoir for implantation has been examined and the effect of temperature and the time of contact of morphine with the different components of the reservoir as well as the sterilization procedure have been investigated. The best stability was observed with a hyperbaric solution in which there was 15 to 20 times less pseudomorphine than in the isobaric solution, which was found to contain 1% pseudomorphine after 1 month of storage at 37 degrees C in the reservoir. Similar solutions stored in ampoules did not degrade.

Chemical Stability of Ziconotide-Clonidine Hydrochloride Admixtures With and Without Morphine Sulfate During Simulated Intrathecal Administration

“…However, combinations of drugs that are chemically unstable may require more frequent clinic visits for pump refills, so the chemical stability of a drug combination is a necessary concern of IT therapy. The stabilities of ziconotide (1), clonidine hydrochloride (6), and morphine sulfate (7) have been characterized for IT monotherapy, but the stabilities of ziconotide–clonidine hydrochloride and ziconotide–clonidine hydrochloride–morphine sulfate admixtures have not been previously reported. The results reported here may help clinicians make informed choices about IT therapy in combination with ziconotide; however, ziconotide is not approved for use in combination therapy, and the clinical implications and potential sequelae associated with the stability observed for these combinations have not been studied and extend beyond the scope of this report.…”

“…The chemical stability of a drug or drug combination is important to consider when contemplating IT therapy, because formulations with lower stability may require more frequent refills. The stabilities of ziconotide (1), clonidine hydrochloride (6), and morphine sulfate (7) have been evaluated in isolation, as have combinations of ziconotide and morphine sulfate (8) and morphine sulfate and clonidine hydrochloride (9); however, the stability of admixtures that pair ziconotide with clonidine hydrochloride, or combine all three drugs, has not been previously determined.…”

Intrathecal Hydromorphone for Chronic Nonmalignant Pain: A Retrospective Study

“…Traditionally, morphine has been the opioid of choice for systemic management of severe pain. The demonstration of the drug's long‐term stability at physiologic temperatures [44] combined with its compatibility with a variety of implantable infusion systems [45] has extended its role, making morphine the mainstay drug for long‐term IT management of severe nonmalignant pain. However, pharmacological complications or reduced analgesic response can diminish its benefit, leaving patients with few options for pain control.…”

Chemical Stability of Admixtures Combining Ziconotide with Morphine or Hydromorphone During Simul ated Intrathecal Administration

“…For IT combination treatment using an implanted pump system, it is first necessary to characterize the chemical stability of a drug combination when stored for prolonged periods at body temperature to determine the compatibility of the drugs and the frequency of pump refills. Although the stabilities of ziconotide (6), morphine (7), and hydromorphone (8) have been evaluated in isolation in implantable internal pumps, the stabilities of ziconotide–morphine or ziconotide–hydromorphone combinations have not been previously determined.…”