Andrews, Danielle Louise;
(2022)
Biopharmaceutics of excipients in paediatric medicines.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Children require palatable medicines. Excipients can improve the acceptability of a formulation, enabling children to take their dose as prescribed to achieve therapeutic exposure to the active pharmaceutical ingredient (API). Sweeteners have traditionally been used but there are safety concerns associated and limited success with highly aversive API. Thus there is a need to identify new approaches, such as those which steer towards a taste-neutral formulation. In order to assess the efficacy of novel taste-masking excipients, appropriate preclinical models are needed. The Brief Access Taste Aversion (BATA) model is one such method which has been used successfully for predicting the aversiveness of API but more work needs to be done to understand the translatability when excipients are present. Some taste-masking excipients can have a negative impact on drug bioavailability and can decrease drug absorption in the gut as shown in adults. Children have a unique gut environment and therefore, there is a need to assess taste-masking excipients for such an effect in age-appropriate models. To further understanding of excipients’ impact on API bioavailability in children, this work achieved the following: 1) identified promising bitter-blockers (sodium acetate, sodium gluconate and Adenosine monophosphate sodium salt) using a novel ranking methodology. The three bitter-blockers were then assessed within liquid formulations but were unable to sufficiently taste-mask therapeutic doses of API. 2) Compared BATA and human data for taste-masking efficacy of a cyclodextrin and a maltodextrin. Differences in species tolerance to the dextrins were seen due to rat neophobia which, if not accounted for, would prevent an accurate pre-clinical prediction of the human response. 3) Compared the effect of sorbitol, a widely used sweetener, on API blood levels in juvenile and adult rats. Sorbitol negatively impacted the bioavailability of model drug in the same way independent of age. The knowledge generated helps inform how taste-masking excipients can be used safely and efficiently in children’s medicines.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Biopharmaceutics of excipients in paediatric medicines |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10155648 |
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