Great efforts have been made to replicate the adult gastrointestinal (GI) environment using in vitro and in silico tools that are now industry standard methods used within pharmaceutical product development. However, all data has been based on adults and there is a need to develop age-appropriate tools that accurately reflect a paediatric population to minimize the burden of clinical testing in this vulnerable population.
Recent work conducted by the PI on this project has characterized paediatric gastric and intestinal fluid and identified differences in the composition compared to similar work conducted in adults. The next step in this work is to better understand how these compositional changes may affect drug solubility and hence drug absorption.
The solubility of many drugs can be enhanced in the presence of GI media that includes colloidal bile and digestion products. In turn, variations in bile salt (BS) and phospholipid concentrations within intestinal fluid have been shown to have significant effects on the solubility of poorly soluble compounds as each BS has a different pKa and molecular aggregation number and therefore behaves differently in terms of colloidal association. Large differences in bile salt concentrations were noted between adult and paediatric fluids which needs to be fully explored to better understand the impact on drug solubility and dissolution which, for poorly soluble drugs can be the rate limiting step for oral absorption.
Whilst well established media are available that simulate the composition of adult intestinal fluid, there are no evidence-based protocols to replicate paediatric intestinal fluid. This work will generate a fasted state simulated paediatric intestinal fluid that will have data demonstrating comparability to aspirated paediatric intestinal fluid.
Thus the aim of this project is to understand how the compositional differences in paediatric intestinal fluid affect drug solubility compared to data from adults and to develop a suitable simulated media to aid in the development of age appropriate medicines.
Biopharmaceutics; pharmaceutical science; Drug discovery, Formulation and Delivery (DDFD)
· Solubility assessment
· Dissolution assessment
· Quantitative analysis using HPLC-UV; HPLC-MS
Excellent students with a strong background in science and a commitment to pharmaceutical research are invited to apply. They should have or realistically expect to obtain, with an Undergraduate Honours degree with a minimum classification of a 1st or equivalent and an English Language qualification for international students. Applicants should have a, chemical engineering, chemistry bioengineering, pharmacy, pharmaceutical sciences, biosciences or biotechnology background and be interested in interdisciplinary research
The project will start in October 2021
Informal enquiries may be made directly to the primary supervisor.
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