Intranasal delivery of morphine.
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 non-injectable opioid product capable of offering patients rapid and efficient pain relief.
Illum
L
L
West Pharmaceutical Services, Drug Delivery and Clinical Research Centre Ltd., Albert Einstein Centre, Nottingham Science and Technology Park, Nottingham, United Kingdom. lisbeth_illum@westpharma.com
Watts
P
P
Fisher
A N
AN
Hinchcliffe
M
M
Norbury
H
H
Jabbal-Gill
I
I
Nankervis
R
R
Davis
S S
SS
D000042:Absorption; D000269:Adhesives; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002686:Chitin / Q000031:analogs & derivatives; D048271:Chitosan; D005079:Excipients; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008863:Microspheres; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D009297:Nasal Mucosa / Q000378:metabolism; D011208:Powders; D012756:Sheep; D012996:Solutions; D013213:Starch
D000269:Adhesives; D000701:Analgesics, Opioid; D005079:Excipients; D011208:Powders; D012996:Solutions; D002686:Chitin; D009020:Morphine; D013213:Starch; D048271:Chitosan