109 - Intranasal morphine  pp. 437-439

Intranasal morphine

By Denis V. Snegovskikh

Image View Previous Chapter Next Chapter



Generic Name: intranasal morphine (morphine mesylate/chitosan)

Trade Name: Rylomine™

Drug Class: opioid analgesic

Manufacturer: Javelin Pharmaceuticals, 125 Cambridge Park Drive Cambridge, MA 02140; Javelin was recently acquired by Hospira, Lake Forest, IL

Chemical Structure: see Figure 109.1

Chemical Name: (5α,6α)-7,8-didehydro-4,5-epoxy-17-methyl morphinian-3,6-diol

Chemical Formula: C17H19NO3; molecular wt 285.34

Introduction

Intranasal (IN) morphine (Rylomine™) is a patient-controlled nasal spray that delivers a single, metered dose of Morphine. Rylomine™ is currently in phase 3 clinical development and may have use as a rapid-acting analgesic in both acute and chronic pain settings.

Description

Intranasal morphine provides rapid analgesic onset (comparable to IV) together with a simple and non-invasive way to control moderate to severe pain. It consists of a combination of active ingredient morphine mesylate and ChiSys delivery system. ChiSys is based on the use of chitosan to evenly disperse and improve morphine absorption through the nasal mucosa.

Chitosan is a cationic linear polysaccharide, composed of two monosaccharides: N-acetyl-d-glucosamine and d-glucosamine linked together by glucosidic bonds. Chitosan is obtained from partial deacetylation of chitin, which originates from shells of crustaceans (e.g. crabs and prawns) and forms positively charged salts when dissolved in inorganic and organic acids. Glutamate salt of chitosan with a mean molecular weight of around 200 kDa and a degree of deacetylation of 80–90% is used for nasal delivery of drugs.

Albin R , Green G , et al. A Phase I Single- and Multiple-Dose Pharmacokinetic Study of Intranasal Morphine in Healthy Volunteers. Javelin Pharmaceuticals, Inc.
Christensen KS , et al. The analgesic efficacy and safety of novel intranasal morphine formulation (morphine plus chitosan), immediate release oral morphine, intravenous morphine and placebo in a postsurgical dental pain model. Pain Med 2008; 107(6):2018–2024.
Fisher A , Green G , et al. A Phase I Absorption Study of Intranasal Morphine in Normal Volunteers. Javelin Pharmaceuticals, Inc.
Hussain A , Faraj J , et el. Hydrolysis of leucine enkephalin in the nasal cavity of the rat– a possible factor in the low bioavailability of nasally administered peptides. Biochem Biophys Res Commun 1985;133:923–928.
Illium L , Dodane V , Iqbal K . Drug Deliv Technonol 2002;2(2):40–43.
Illum L , Watts P , et al. Intranasal delivery of morphine. J Pharmacol Exp Ther 2002;301:391–400.
Lee VH . Enzymatic barriers to peptide and protein absorption. Crit Rev Ther Drug Carrier Syst 1988:5:69–97.
Muzzarelli RAA . Chitin. In Muzzarelli RAA , ed. Natural Chelating Polymers: Alginic Acid, Chitin and Chitosan. New York: Pergamon Press, 1973, pp. 83–252.
Schipper NG , Verhoef JC , Merkus FW . The nasal mucociliary clearance: relevance to nasal drug delivery. Pharm Res 1991;8:807–814.
Sheckler MT , et al. Nasal Delivery of Analgesics. 2005. Available at: http://www.ondrugdelivery.com/publications/NASAL%20FINAL%20Lo-res.pdf.
Stoker DG , et al. Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate-to-severe pain following orthopedic surgery. Pain Med 2008;9:3–12.