Formulation and characterisation of nasal spray pharmaceutical compositions

• Main Author: Barnier, Céline
• Published: University of Leeds 2011
• Subjects: 615.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558798

Spray technology is used in the delivery of pharmaceutical ingredients through the nose or lungs. There is an ongoing requirement to establish a more in-depth understanding of the spray properties and their dependence on pharmaceutical formulations, 011 device parameters. on patients' operation and their influence on the resulting delivery sites. The study presented here consisted of three phases aimed at furthering the understanding of the properties of nasal spray formulations from a physico-chemical point of view. This includes the relationship between the suspension properties, the spraying behaviour and the effect 011 the deposition pattern within the nasal cavity. Phase 1: A commercially available nasal spray suspension. a placebo and laboratory formulation. were characterised for rheological properties and spray behaviour using high speed imaging. Thi work demonstrated the shear thinning and viscoelastic properties of the sample, as well as strain hardening behaviour occurring above the extensional strain of 3.8, 105 5'. It was also found, from the imaging techniques employed. that the spray formed a hollow cone and, the formation of droplets from the fluid sheet could be observed. Results from a set of Box-Behnken and Mixture design of experiment showed that the EDTA influenced the rheological properties of the suspensions and. the interactions between BKC and dextrose affected the spray behaviour. Phase 2: A range of formulations modified with small amounts of polymeric additives (30 - 200ppm), polyethylene oxide and hydroxypropyl methylcellulose, were developed to assess the influence of such polymers on spray properties. lt was found that the addition of PEO broadened the droplet size distributions and reduced the spray dimensions, whereas the addition of HPMC did not significantly affect the spray properties. Phase 3: The final phase involved the study of the in-vivo deposition of the modified formulations, using a human nasal cavity model, under three different forced air flow rates. This study aimed at observing the influence of formulation variation on intranasal deposition. It was found that the addition of PEO increased the deposition of the droplet ill the nasal valve region and, that the forced air flow rate did not affect the profile of deposition. The un-modified suspension deposited mainly in anterior region of the nose without forced air flow, however, as the forced air flow rate increased. the droplets were swept further to deposit in the nasal valve region and turbinates region.