Crystal engineering new, more effective medicines.

BACKGROUND

Neglected Tropical Diseases (NTDs) – a diverse group of infectious diseases – continue to thrive across low- income populations. Labelled 'neglected' as drug development to formulate new and more suitable drugs is scarce. The drugs used to treat these conditions are often inadequate and have many formulation problems due to their solubility limited bioavailability, resulting in large, difficult to swallow tablets which taste terribly. But such is the desperation and the need to take these life-saving medicines that many children and elderly choke whilst taking them.

SCIENTIFIC TOOLKIT

Crystal engineering is a term used to describe the study of the relationship between the structure and function of crystalline materials. The field has evolved to enable modification of the fundamental crystalline framework (and thus properties) of drug products. The aim of crystal engineering is to enable the design of materials which can overcome common material problems such as poor solubility or compaction.

Crystal engineering will enable the synthesis of novel cocrystal systems (i.e., the design and synthesis of solid-state structures with desired properties based on the use of intermolecular interactions). Cocrystals are crystalline solids where two or more components (i.e., coformers) have been combined in a fixed 'stoichiometric' ratio to form a new material. Most drugs on the market are crystalline solids with the drug packed in a specific arrangement (or more accurately, structure) which confers distinct properties. As such, formulation optimisation can be achieved using crystal engineering.

As each crystal form is expected to have its own physicochemical properties, crystal engineering will enable the synthesis of novel drug formulations which bring about dramatic changes to drug properties (e.g., solubility and stability). Additionally, as the number of potential cocrystal forms is potentially endless, crystal engineering can enable the refinement of drug properties by adjusting the crystal structure in a systematic way.

SCIENTIFIC QUESTIONS

1. Can we employ crystal engineering methodology to reduce the overall size of NTD drug formulations?

2. Can crystal engineering help us modify compaction behaviour in a quantifiable way?

3. Can these new forms also modulate other important properties such as solubility and taste?

Previously, Dr Kavanagh has illustrated that cocrystallisation may be a more effective approach to develop high-drug load multidrug powders for direct compression. In such cases, less excipients are needed to attain adequate tabletability so that smaller tablets can be prepared to deliver the same amount of drug. This concept could synergise with the work described above to reduce the overall size of the final dosage form. From a scientific perspective, there remains a mismatch between shear planes identified through energy framework analysis and expected plasticity which was uncovered in our study. You will work on Dr Kavanagh's EPSRC funded lab to advance these scientific objectives.