Application of biorelevant saliva-based dissolution for optimisation of orally disintegrating formulations of felodipine

Ali, Joseph; Zgair, Atheer; Hameed, Ghaidaa S.; Garnett, Martin C.; Roberts, Clive J.; Burley, Jonathan C.; Gershkovich, Pavel

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 minutes. On the other hand, salivabased dissolution showed that percentage release of felodipine was only 0.2% after 10 minutes 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.

Citation

Ali, J., Zgair, A., Hameed, G. S., Garnett, M. C., Roberts, C. J., Burley, J. C., & Gershkovich, P. (2019). Application of biorelevant saliva-based dissolution for optimisation of orally disintegrating formulations of felodipine. International Journal of Pharmaceutics, 555, 228-236. https://doi.org/10.1016/j.ijpharm.2018.11.051

• Journal Article Type: Article
• Acceptance Date: Nov 17, 2018
• Online Publication Date: Nov 19, 2018
• Publication Date: Jan 30, 2019
• Deposit Date: Nov 19, 2018
• Publicly Available Date: Nov 20, 2019
• Journal: International Journal of Pharmaceutics
• Print ISSN: 0378-5173
• Electronic ISSN: 1873-3476
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 555
• Pages: 228-236
• DOI: https://doi.org/10.1016/j.ijpharm.2018.11.051
• Keywords: Biorelevant dissolution; Human saliva; Oral cavity; Felodipine; Orally disintegrating tablets
• Public URL: https://nottingham-repository.worktribe.com/output/1284067
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0378517318308755?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: Application of biorelevant saliva-based dissolution for optimisation of orally disintegrating formulations of felodipine; Journal Title: International Journal of Pharmaceutics; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ijpharm.2018.11.051; Content Type: article; Copyright: © 2018 The Authors. Published by Elsevier B.V.
• Contract Date: Nov 19, 2018