Thesis

In-vitro and in-vivo properties of a lyophilised nasal dosage system

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Awarding institution
  • University of Strathclyde
Date of award
  • 2003
Thesis identifier
  • T10764
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Department, School or Faculty
Abstract
  • The aim of this research was to examine the in-vitro and in-vivo properties of a lyophilised hydroxyproylmethylcellulose (HPMC) nasal insert dosage formulation, and assess its potential as a bioadhesive nasal formulation. In-vitro adhesive tests performed using a Texture Analyser gave variable results, prompting the development of novel dynamic adhesion and sliding adhesion tests designed to mimic the movement of the formulation over the nasal mucosa. Results indicated that increasing polymer molecular weight and concentration increased adhesion to a synthetic mucosal surface (agar), while over hydration resulted in a decrease in adhesion. The use of a confocal laser scanning microscope (CLSM) to assess rate of water ingress into lyophilisates is described, with formulations showing an initial rapid rate of hydration, followed by a steady state rate of water ingress. Dynamic water vapour sorption studies demonstrated a high vapour sorption capacity, and a recrystallisation of amorphous mannitol, with scanning electron microscope (SEM) images depicting the effect of altering the relative mannitol and HPMC concentrations on the surface structure of the lyophilisates. SEM images also displayed the high internal porosity of the formulations, with pore size decreasing with increasing HPMC concentration, and showing correlation with rate of water ingress determined by the CLSM and an initial phase of linear insulin release demonstrated in dissolution studies. In-vivo studies in sheep showed that the nasal insert increased bioavailability of nicotine over conventional spray and powder formulations, giving prolonged plasma nicotine levels. In-vivo nasal insulin absorption was not enhanced by the nasal insert, despite attempts to improve bioavailability by manipulating the formulation. A proposal for a study of the insert formulation in human volunteers is outlined. In conclusion, the lyophilised nasal insert formulation displays adhesive properties influenced by polymer concentration, and increased nicotine bioavailability in sheep, but may not be suitable for nasal insulin administration.
Advisor / supervisor
  • Stevens, Howard N. E.
Resource Type
DOI
EThOS ID
  • uk.bl.ethos.275120

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