Development and optimisation of simulated salivary fluid for biorelevant oral cavity dissolution.

Drug release within the oral cavity can be of paramount importance for formulations that are designed for specific purposes such as taste-masking, faster onset of therapeutic action, localization of treatment or avoidance of first-pass metabolism. Preclinical methods for assessment of dissolution in the oral cavity are necessary for design and development of these formulation but currently there is no consensus on what variables should be defined to achieve biorelevance in these tests. In this study, biorelevant simulated salivary fluids (SSFs) that can be uniformly applied for oral cavity dissolution testing were developed. Unstimulated saliva (US) SSF and stimulated saliva (SS) SSF were separately developed since the two states significantly differ. Physicochemical properties including pH, buffer capacity, surface tension and viscosity were assessed during development and optimised to mimic human saliva (HS). In order to account for the salivary proteins in HS, use of bovine submaxillary mucin (BSM) and porcine gastric mucin (PGM) in SSFs was evaluated. Following optimisation of the SSFs, biorelevance of the developed SSFs to HS was assessed by their comparative physicochemical properties as well as dissolution profiles of three diverse model compounds (sildenafil citrate, efavirenz, and caffeine) which showed comparable profiles between the SSFs and HS. This work addresses the lack of uniformed biorelevant dissolution media for oral cavity dissolution studies and provides a basis for standardised dissolution tests that provide consistency and harmonisation in future oral cavity dissolution studies. We envisage that this will have a positive impact on the development of new medicines that require functionality in the oral cavity.