Elucidating bioadhesive processes in nasal drug delivery systems

Mucoadhesive formulations have been used to increase the residence time and improve bioavailability of nasal dosage forms. The exact nature of the interplay between formulations and the mucus layer has not been defined, although theories have been proposed suggesting that certain characteristics are required for optimum mucoadhesivity. This thesis presents an investigation into the effects of the properties of excipients in nasal formulations on their mucoadhesive performance. The main factors that were investigated included molecular weight, concentration, crosslinking density, charge, and viscosity. It was established using rotational and oscillation rheology that the polymeric formulations with the highest molecular weight expressed the highest viscosity. Thixotropy, a vital property in mucoadhesion, was also assessed. The greatest thixotropy was found with polymers of increasing molecular weight whereas low molecular weight polymers exhibited little or no thixotropy. As expected, high molecular weight polymers produced strongly gelled networks; a requirement for mucoadhesion. Mucoadhesive interactions between polymers and mucin were analysed using standard rheology and microrheology. Greater synergy was found with high molecular weight, linear, ionic polymers; factors which allow for improved chain interactions. Texture analysis of the formulations confirmed that the adhesive forces increased for higher molecular weight, ionic polymers. In conclusion, it was found that a combination of a high molecular weight, increased viscosity, charge, and a moderate level of crosslinking are all favourable properties in a polymeric nasal spray. The formulation of a mucoadhesive dosage form with these characteristics may improve the retention time of the formulation within the nose, resulting in an increased opportunity for drug absorption and thus greater bioavailability.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2014

Author dc:creator

• Armstrong, Michelle

DOI

10.48730/6nbf-yx94

Identifier

T13710

OAI identifier oai:identifier

oai:strathclyde:2r36tx551