Comparative Bioavailability of Sustained-Release Morphine Sulfate Capsules versus Pellets

The management of pain in terminally ill cancer patients with difficulty swallowing

“…48 A recent randomized, single-dose, open-label, four-way crossover study in 25 healthy male and female volunteers evaluated whether 50-mg sustained-release morphine sulfate capsules swallowed whole were bioequivalent to 50-mg doses of sustained-release morphine sulfate pellets sprinkled on applesauce. 16 This study confirmed the results of earlier in vitro studies 11 that showed the rate of sustained-release morphine sulfate pellets was not affected when the pellets were sprinkled on applesauce. More specifically, the investigators concluded that sustained-release morphine sulfate pellets administered via the sprinkling method were bioequivalent to the use of sustained-release morphine sulfate capsules swallowed whole.…”

“…The noninvasive routes include the oral, rectal, transdermal, sublingual, and, most recently, sprinkling and transmucosal administration. 15, 16 Oral formulations include immediate-release and sustained-release tablets and capsules, solutions, lozenges, and sustainedrelease pellets suitable for sprinkling. Central or localized routes, such as intrathecal and epidural administration, will not be addressed in this paper.…”

“…In addition, the investigators stated that this form of administration may offer a significant advantage in the management of patients with cancer pain, particularly those with general debility or difficulty swallowing tablets. 16 The sprinkling method for sustained-release morphine administration allows practitioners to use morphine, the opioid of choice in hospice patients, for longer periods of time in the management of end-stage cancer pain. Furthermore, the administration of sustained-release morphine by sprinkling obviates the need for transdermal fentanyl and infusional morphine in many settings, yet still allows morphine dosage titration to analgesic effect every 24 to 48 hours.…”

KADIAN® (morphine sulfate extended-release) Capsules for treatment of chronic, moderate-to-severe, nonmalignant pain

“…Similar results were seen after 30 min of exposure to water followed by administration through a 16 French gastrostomy tube (19). Bioequivalence was confirmed in a randomised, single‐dose, four‐way crossover study in which KAPANOL ® capsules swallowed whole were shown to be bioequivalent to KAPANOL ® pellets sprinkled over applesauce, under both fed and fasted conditions (20).…”

Treatment of chronic moderate-to-severe non-malignant pain with polymer-coated extended-release morphine sulfate capsules

“…Accordingly, KRONUS-MSP was a prospective, randomized, open-label, blinded endpoint (PROBE) study 24 using polymer-coated extended-release morphine sulfate capsules (P-ERMS) (KADIAN), an opioid with demonstrated efficacy in cancer pain 25 . P-ERMS has a relatively flat concentration-time curve over a 12-or 24-h dosing interval [25][26][27][28] , and is the only opioid formulation currently indicated in the US for either a once-or twice-daily dosing interval. The study included more than 200 sites in community settings in the US, and included patients with all non-malignant pain types, regardless of etiology.…”