Intranasal Delivery of Morphine

• Published in: The Journal of pharmacology and experimental therapeutics 2002-04, Vol.301 (1), p.391-400
• Main Authors: Illum, L, Watts, P, Fisher, A N, Hinchcliffe, M, Norbury, H, Jabbal-Gill, I, Nankervis, R, Davis, S S
• Format: Article
• Language: English
• Subjects: Absorption; Adhesives; Administration, Intranasal; Adolescent; Adult; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Analgesics, Opioid - pharmacokinetics; Animals; Area Under Curve; Chitin - analogs & derivatives; Chitosan; Excipients; Female; Humans; Injections, Intravenous; Male; Microspheres; Morphine - administration & dosage; Morphine - adverse effects; Morphine - pharmacokinetics; Nasal Mucosa - metabolism; Powders; Sheep; Solutions; Starch
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.301.1.391

Morphine administered nasally to humans as a simple solution is only absorbed to a limited degree, with a bioavailability of the order of 10% compared with intravenous administration. This article describes the development of novel nasal morphine formulations based on chitosan, which, in the sheep model, provide a highly increased absorption with a 5- to 6-fold increase in bioavailability over simple morphine solutions. The chitosan-morphine nasal formulations have been tested in healthy volunteers in comparison with a slow i.v. infusion (over 30 min) of morphine. The results show that the nasal formulation was rapidly absorbed with a T max of 15 min or less and a bioavailability of nearly 60%. The shape of the plasma profile for nasal delivery of the chitosan-morphine formulation was similar to the one obtained for the slow i.v. administration of morphine. Furthermore, the metabolite profile obtained after the nasal administration of the chitosan-morphine nasal formulation was essentially identical to the one obtained for morphine administered by the intravenous route. The levels of both morphine-6-glucuronide and morphine-3-glucuronide were only about 25% of that found after oral administration of morphine. It is concluded that a properly designed nasal morphine formulation (such as one with chitosan) can result in a noninjectable opioid product capable of offering patients rapid and efficient pain relief.