Is rat a good model for assessment of particulate-based taste-masked formulations?

Ali, Joseph; Chiang, Manting; Lee, Jong Bong; Voronin, Gregory O.; Bennett, Joanne; Cram, Anne; Kagan, Leonid; Garnett, Martin C.; Roberts, Clive J.; Gershkovich, Pavel

Abstract

Recently there has been an increased interest to develop specialised dosage forms that are better suited to specific patient populations, such as paediatrics and geriatrics. In these patient populations the acceptability of the oral dosage form can be paramount to the products success. However, many active pharmaceutical Ingredients (APIs) are known to cause an aversive taste response. One way to increase the acceptability and to enhance the palatability of the formulation is to design coated taste-masked particulate-based dosage forms. The masking of poorly tasting drugs with physical barriers such as polymer coatings can be utilised to prevent the release of drug within the oral cavity, thus preventing a taste response. However, currently, there are few assessment tools and models available to test the efficiency of these particulate-based taste-masked formulations. The rat brief access taste aversion model has been shown to be useful in assessment of taste for liquid dosage forms. However, the applicability of the rat model for particulate-based taste masked formulations is yet to be assessed. It is not understood whether dissolution, solubility and thus exposure of the drug to taste receptors would be the same in rat and human. Therefore, rat saliva must be compared to human saliva to determine the likelihood that drug release would be similar within the oral cavity for both species. In this study rat saliva was characterised for parameters known to be important for drug dissolution, such as pH, buffer capacity, surface tension, and viscosity. Subsequently dissolution of model bitter tasting compounds, sildenafil citrate and efavirenz, in rat saliva was compared to dissolution in human saliva. For all parameters characterised and for the dissolution of both drugs in rat saliva, a substantial difference was observed when compared to human saliva. This discrepancy in saliva parameters and dissolution of model drugs suggests that preclinical taste evaluation of particulate-based taste-masked formulations suggests rat is not a good model for predicting taste of solid dosage forms or undissolved drug where dissolution is required. Alternative preclinical in vivo models in other species, or improved biorelevant in vitro models should be considered instead.

Citation

Ali, J., Chiang, M., Lee, J. B., Voronin, G. O., Bennett, J., Cram, A., …Gershkovich, P. (2020). Is rat a good model for assessment of particulate-based taste-masked formulations?. European Journal of Pharmaceutics and Biopharmaceutics, 146, 1-9. https://doi.org/10.1016/j.ejpb.2019.11.001

• Journal Article Type: Article
• Acceptance Date: Nov 6, 2019
• Online Publication Date: Nov 11, 2019
• Publication Date: 2020-01
• Deposit Date: Nov 12, 2019
• Publicly Available Date: Nov 26, 2019
• Journal: European Journal of Pharmaceutics and Biopharmaceutics
• Print ISSN: 0939-6411
• Electronic ISSN: 1873-3441
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 146
• Pages: 1-9
• DOI: https://doi.org/10.1016/j.ejpb.2019.11.001
• Keywords: Rat saliva; Oral cavity; Dissolution; Particulate-based taste-masked formulation
• Public URL: https://nottingham-repository.worktribe.com/output/3232478
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0939641119312925
• Additional Information: This article is maintained by: Elsevier; Article Title: Is rat a good model for assessment of particulate-based taste-masked formulations?; Journal Title: European Journal of Pharmaceutics and Biopharmaceutics; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ejpb.2019.11.001; Content Type: article; Copyright: © 2019 The Authors. Published by Elsevier B.V.