In vivo evaluation of nicotine lyophilised nasal insert in sheep

The nasal route offers an attractive means of delivering a drug directly to the systemic circulation and avoiding hepatic first-pass metabolism, although rapid mucociliary clearance can be detrimental to nasal absorption. The in vitro and in vivo characteristics of a nasal insert formulation prepare...

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Bibliographic Details
Published in:International journal of pharmaceutics 2005-11, Vol.304 (1), p.72-82
Main Authors: McInnes, Fiona J., Thapa, Panna, Baillie, Alan J., Welling, Peter G., Watson, David G., Gibson, Ian, Nolan, Andrea, Stevens, Howard N.E.
Format: Article
Language:English
Subjects:
Adhesion
Administration, Intranasal
Adsorption
Aerosols
Animals
Biological and medical sciences
Biological Availability
Delayed-Action Preparations
Excipients - chemistry
Freeze Drying
Gels
General pharmacology
HPMC
Injections, Intravenous
Lactose - analogs & derivatives
Lactose - chemistry
Medical sciences
Methylcellulose - analogs & derivatives
Methylcellulose - chemistry
Nasal
Nasal Mucosa - metabolism
Nicotine
Nicotine - administration & dosage
Nicotine - chemistry
Nicotine - pharmacokinetics
Oxazines
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Porosity
Powders
Random Allocation
Sheep
Solubility
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Summary:The nasal route offers an attractive means of delivering a drug directly to the systemic circulation and avoiding hepatic first-pass metabolism, although rapid mucociliary clearance can be detrimental to nasal absorption. The in vitro and in vivo characteristics of a nasal insert formulation prepared by lyophilisation of a viscous HPMC gel solution designed to overcome this problem were studied. In vitro release of nicotine from the lyophilised insert was compared with powder and spray formulations. Stability and characterisation studies were carried out using dynamic vapour sorption, scanning electron microscopy and HPLC analysis. Nicotine formulations were administered to eight wether sheep in a randomised four-way cross-over study, and plasma nicotine assessed comparing the nasal insert formulation with conventional nasal powder, nasal spray and IV doses. In vitro release studies demonstrated prolonged nicotine release from the nasal insert formulation compared to a powder and liquid. In vivo plasma profiles appeared to show prolonged plasma nicotine levels compared to the conventional formulations, although T max, C max and AUC parameters for the insert were not significantly different due to high variability in the pharmacokinetic data. In conclusion, the nasal insert displayed a promising prolonged plasma profile, which must be investigated further to provide statistical significance to prove the effect.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2005.07.025