Application of biorelevant saliva-based dissolution for optimisation of orallydisintegrating formulations of felodipine

Abstract

The oral cavity is of great importance to the performance of orally retained formulations, including: orally
disintegrating tablets, taste-masked formulations, and buccal/sublingual delivery systems. With regards to in vitro 
dissolution assessment of these dosage forms, human saliva should be represented by the dissolution media.
Currently there is no general consensus regarding oral cavity dissolution. In this study pooled human saliva was
characterised and utilised as dissolution media for biorelevant oral cavity dissolution studies and to assess drug
release. Lipophilic drug felodipine with challenging biopharmaceutical properties was selected for assessment in oral 
cavity dissolution studies. These saliva dissolution studies investigated for the first time how biorelevant dissolution 
can be implemented as a screening tool to guide the formulation development process and to predict dosage form
performance within the mouth. In this study a combination of three dissolution enhancement strategies (cryomilling, 
solid dispersion, and inclusion complexation) were employed to eventually increase the concentration of felodipine in 
saliva 150-fold. Using this successful formulation strategy orally disintegrating tablets of felodipine were produced. 
Interestingly, the percentage release of felodipine in compendial dissolution apparatus was shown to be over 80% 
after 10 min. On the other hand, saliva-based dissolution showed that percentage release of felodipine was only
0.2% after 10 min using the same formulation. This discrepancy in drug release between dissolution media
highlights the need for biorelevant dissolution apparatus for the oral cavity to reliably assess performance of
relevant dosage forms in vitro