TIM-1 Model: Predicting Absorbable Dose & Crystallisation Strategy

Using the TIM-1 artificial gastrointestinal model to determine the maximum absorbable dose based on degree of solubility enhancement required for a series of model drug substance and technologies to induce supersaturation. Generate sufficient datasets to build a model for prediction of population-based parameters that influence overall bioaccessible fraction to inform the formulation and crystallisation strategy for the molecule

The intestinal solubility of a series of drugs has been measured in a suite of simulated fluids at Strathclyde (Abuhassan, Q., Silva, M.I., Tamimi, R.A.-R., Khadra, I., Batchelor, H.K., Pyper, K., Halbert, G.W. A novel simulated media system for in vitro evaluation of bioequivalent intestinal drug solubility (2024) European Journal of Pharmaceutics and Biopharmaceutics, 199, art. no. 114302,

DOI: 10.1016/j.ejpb.2024.114302).

This data shows the variability in solubility required to maximise the absorption. This data set can be used to explore the level of solubility enhancement required to limit precipitation of the drug in the GI tract. The TIM apparatus can be used as a physical system to generate observed data and this can be compared to predictions made either using existing commercial software (SimCYP, GastroPlus, gPROMS ForumlatedProducts) or based on recent data driven approaches (https://doi.org/10.1038/s42256-021-00357-4) .

The lab work will requrie the development and manufacture or acquisition of existing commercial dosage forms to generate the TIM data. There will also be a need to undertake some other simple analysis to under pin the work (eg solubility assessment in a range of SIF).