Taste masking medicines for children through crystal engineering

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Unacceptable palatability is a major obstacle in the development of medicines for infants and toddlers, as it often impedes patient adherence. The masking of bad taste is therefore widely recognized by regulatory authorities as a key aspect in modern paediatric drug development. and legislation in Europe and USA is currently requiring and rewarding the development of palatable paediatric medicines. The proposed PhD research project aims to develop a crystal-engineering approach to bitter-taste masking of drug molecules commonly used in paediatric oral formulations (e.g. flucloxacillin and prednisone). The approach relies on the construction of multi-component crystals involving a bitter-tasting drug and a taste-masking agent, whereby the molecules are held together by hydrogen bonds. The taste-masking agent is either a pharmaceutically acceptable compound taste blocker, or a molecule that hydrogen-bonds with the drug in a fashion that prohibits any interaction between the drug and the taste receptors. The formation of the described multi-component crystals (i.e. cocrystals) can be achieved fast (<1h), with the use of minimal amounts of solvents (or even without) and in large quantities (>1kg) without the use of specialised equipment. The taste of the cocrystals will be assessed in vivo, including using the Brief Access Taste Aversion model. Moreover, pharmaceutical studies will assess if cocrystals could enhance material properties (e.g. tabletability) in relation with handling, manufacturability and potentially clinical performance ensuring that the outcomes of this research are fully translational.The research programme will explore the use of crystal engineering tactics in paediatric drug formulation, and aim to develop pharmaceutical cocrystals for palatable medicines. The research programme will involve the following:- Selection of active pharmaceutical ingredients (APIs) relevant to paediatric health care and identify a set of suitable cocrystal formers using data base surveys and cheminformatics- Completion of cocrystal screens for each API and finish the solid-state characterisation of the prepared cocrystals- Evaluation pharmacokinetic properties of relevant cocrystals and assess their taste using the rat brief-access taste aversion (BATA) model - Develop structure-property relationships that will enable development of guidelines for the design of palatable cocrystal using principles of crystal engineering.