Development of biorelevant simulated salivary fluids for application in dissolution testing

• Main Author: Gittings, Sally
• Published: University of Nottingham 2017
• Subjects: 615.7; RS Pharmacy and materia medica
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.719462

Conventional adult dosage forms such as tablets and capsules are often not suitable for the paediatric and geriatric population due to either swallowing difficulties or a requirement for tailored dosing to meet individual needs. Alternative oral formulations such as orally disintegrating tablets (ODTs) are available; however these usually require the incorporation of taste masking techniques. One approach to taste masking is to reduce contact between the bitter active pharmaceutical ingredient (API) and taste buds. This may be achieved by hindering release in the oral cavity using reverse enteric polymeric coatings. In vitro dissolution testing can be employed to elucidate taste masking capability by quantifying release of the API in simulated oral cavity conditions. This provides a robust analytical approach circumventing the expense and ethical challenges associated with human taste testing panels or animal testing. To achieve taste masking, drug release should be below the bitterness threshold concentration of the API. A vast array of dissolution methodologies has been employed in the evaluation of taste masked formulation performance in literature, with little agreement between approaches, and a lack of biorelevance. For optimal predictability, the dissolution test should be biorelevant and the dissolution media should mimic human saliva as closely as possible. Human saliva is thus a biological fluid of great importance in the field of dissolution testing. However, until now, no consensus has been reached on its key characteristics relevant to dissolution testing. As a result, it is difficult to select or develop an in vitro dissolution medium to best represent human saliva. In this thesis, for the first time, the pH, buffer capacity, surface tension, viscosity and flow rate of both unstimulated (US) and stimulated (SS) human saliva were investigated with a sufficient number of participants to generate statistically meaningful results (Chapter 3). This provides a platform of reference for future dissolution studies using simulated salivary fluids (SSFs).