Enhancement of nasal delivery of a renin inhibitor in the rat using emulsion formulations

Nasal absorption of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L-leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (I), a renin inhibitor, was evaluated in two rat nasal models, one involving surgery and the other requiring no surgical intervention. Oleic acid/monoolein e...

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Bibliographic Details
Published in:Pharmaceutical research 1992-08, Vol.9 (8), p.1024-1028
Main Authors: KARARLI, T. T, NEEDHAM, T. E, SCHOENHARD, G, BARON, D. A, SCHMIDT, R. E, KATZ, B, BELONIO, B
Format: Article
Language:English
Subjects:
Administration, Intranasal
Animals
Biological and medical sciences
Biological Availability
Chromatography, High Pressure Liquid
Dipeptides - administration & dosage
Dipeptides - pharmacokinetics
Emulsions
General pharmacology
Glycerides - chemistry
Male
Medical sciences
Morpholines - administration & dosage
Morpholines - pharmacokinetics
Nasal Mucosa - drug effects
Oleic Acid
Oleic Acids - chemistry
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Renin - antagonists & inhibitors
Solubility
Taurocholic Acid - chemistry
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Summary:Nasal absorption of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L-leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (I), a renin inhibitor, was evaluated in two rat nasal models, one involving surgery and the other requiring no surgical intervention. Oleic acid/monoolein emulsion formulations were tested along with a control PEG 400 solution. The percent absolute bioavailability of the compound was enhanced from 3-6% (PEG 400 solution) to 15-27% when the emulsion formulations were used. The different nasal model techniques (with and without surgery) did not produce any statistical difference in the absolute bioavailability values for I. Emulsion formulations did not produce appreciable damage as assessed morphologically. It is suggested that emulsion formulations containing membrane adjuvants such as oleic acid and monoolein can be used to enhanced the nasal delivery of low-bioavailable, lipid-soluble drugs.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1015850310589