An Investigation of Oily Formulations for the Management of Xerostomia
The physicochemical properties of natural saliva are responsible for many of its functions, yet an understanding about how the physicochemical properties of a saliva substitute influence clinical efficacy is limited. The aim of this thesis was to investigate oily formulations as potential saliva substitutes for individuals with xerostomia. Physicochemical properties of different compositions were investigated with an emphasis on rheology, as viscoelasticity was hypothesised to be important in developing a retentive saliva substitute that could lubricate the dynamic environment of the oral cavity. Further, a pilot study was conducted on healthy participants to determine the taste acceptability and retention of a selected oily formulation. An initial investigation into the rheological properties of natural saliva confirmed that unstimulated saliva was shear thinning whereas stimulated saliva was a Newtonian fluid. In addition, natural whole saliva had a tan δ that was greater than one at low frequencies, indicating a higher contribution of viscous behaviour compared to elastic behaviour. At oscillatory frequencies greater than 5.2 Hz, tan δ was less than one, indicating that elastic behaviour was dominant. This was not observed in the commercially available saliva substitute (OralBalance®), which had a tan δ less than one, independent of frequency. Although this commercial saliva substitute was shear thinning, apparent viscosity was significantly higher at any shear rate (p < 0.01). Emulsions, which contain both oil and water, were hypothesised to offer advantages over current saliva substitutes by combining the lubricating properties of oil with the acceptability of water. Compositions were prepared with food- and pharmaceutical- grade excipients and characterised using pseudo-ternary phase diagrams and polarised light microscopy. These investigations confirmed that the physical features of the formulations depended on excipient selection as well as the composition of each component. Compositions of rice bran oil, water and a surfactant mix of soy lecithin and propylene glycol at a weight ratio of 1:1 w/w, which formed coarse emulsions that were o/w, w/o or pseudo-bicontinuous depending upon their composition, were selected for further characterisation. Viscoelastic properties were analysed using both flow and oscillatory rheology and were found to be influenced by composition, frequency and shear stress. This research demonstrated that the rheologically structured compositions exhibited shear thinning flow behaviour, although apparent viscosity was higher than for natural saliva at any shear rate. Interestingly, threshold frequencies were determined for some compositions where a peak in tan δ was observed, coinciding with a reduction in the storage modulus and increase in loss modulus. Compositions were able to maintain their rheological structure in the presence of up to 50% w/w water. Those with a rice bran oil, surfactant mix (lecithin and propylene glycol 1:1 w/w) and water ratio of 2:3:5 and 2:2:6 (w/w), exhibited frequency-dependent behaviour similar to that of natural saliva, where tan δ was greater than one at low frequencies and less than one at higher frequencies. These compositions were of particular interest. Viscous behaviour at low frequencies was hypothesised to offer lubrication in the oral cavity at rest whereas elastic behaviour at higher frequencies was thought to promote retention during higher shear tasks such as speaking and eating. Finally, the clinical application of a selected composition was trialled in a clinical study and showed that the retention of the emulsion immediately after rinsing was 8.34% higher than water (p = 0.003) and 4.57% higher than a 1% w/v methylcellulose substitute (p = 0.06). Information gained from this study will greatly facilitate the future development of successful saliva substitutes, which in turn will alleviate the terrible burden of morbidity suffered by xerostomia patients.
Advisor: Medlicott, Natalie J; Kieser, Jules A
Degree Name: Doctor of Philosophy
Degree Discipline: School of Pharmacy
Publisher: University of Otago
Keywords: xerostomia; emulsion; saliva substitutes; rheology; viscoelasticity; salivary hypofunction
Research Type: Thesis