Elucidating bioadhesive processes in nasal drug delivery systems

Michelle Armstrong

Research output: ThesisDoctoral Thesis

Abstract

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.
LanguageEnglish
QualificationPhD
Awarding Institution
  • Faculty Of Science
Supervisors/Advisors
  • Wilson, Clive, Supervisor
  • Boyter, Anne, Supervisor
Thesis sponsors
Award date11 Mar 2014
Publisher
Publication statusPublished - Mar 2014

Fingerprint

Drug Delivery Systems
Nose
Molecular Weight
Polymers
Viscosity
Rheology
Dosage Forms
Biological Availability
Nasal Sprays
Excipients
Mucins
Mucus
Adhesives
Pharmaceutical Preparations

Keywords

  • drug delivery
  • nasal drugs
  • bioadhesion

Cite this

Armstrong, M. (2014). Elucidating bioadhesive processes in nasal drug delivery systems. University of Strathclyde.
Armstrong, Michelle. / Elucidating bioadhesive processes in nasal drug delivery systems. University of Strathclyde, 2014.
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Armstrong, M 2014, 'Elucidating bioadhesive processes in nasal drug delivery systems', PhD, Faculty Of Science.

Elucidating bioadhesive processes in nasal drug delivery systems. / Armstrong, Michelle.

University of Strathclyde, 2014.

Research output: ThesisDoctoral Thesis

TY - THES

T1 - Elucidating bioadhesive processes in nasal drug delivery systems

AU - Armstrong, Michelle

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

KW - drug delivery

KW - nasal drugs

KW - bioadhesion

M3 - Doctoral Thesis

PB - University of Strathclyde

ER -

Armstrong M. Elucidating bioadhesive processes in nasal drug delivery systems. University of Strathclyde, 2014.