Drug discovery is a complex process, but there are many ways improvements can be made. Three of the issues facing drug developers – poor solubility, predicting pharmacokinetics and synthetic route selection – can all be addressed in advance, making the whole process run more effectively.
A key tool for poor solubility is solid form screening. As a bridge between drug substance and drug product, its aim is to identify the optimal solid form. This will often be a crystal polymorph, but this is not the only possibility. When determining the crystallisation process, it is important to consider the yield, the particle size, and the impurity profiles, as well as how the crystals will behave on formulation.
Here at Lonza, the solid form screening workflow starts with the careful characterisation of the API ahead of a survey of crystal forms which, typically, takes three or four weeks and requires 2–5g of material. Then, if necessary, further screening of potential salts or cocrystals can be done, or an amorphous form developed.
Physiologically based pharmacokinetic (PBPK) modelling is a powerful tool to gain an understanding of how a candidate drug might behave in vivo, notably its absorption characteristics. Lonza uses ADMET Predictor and GastroPlus software in combination with a variety of both bespoke and off-the-shelf lab tests in its PBPK modelling service. It is an extremely useful tool in predicting problems in advance, and if the answer is in place early, it can minimise delays and assist with meeting accelerated timelines.
Route scouting is a tool that can explore the options, and help process chemists identify the optimal synthetic route more quickly. Here at Lonza, the company uses artificial intelligence and machine learning algorithms alongside Lonza's experts’ knowledge and experience, plus in-house insight into supply chain availability and raw material properties.