It is critical to get the formulation of a new drug right to ensure it is easy to administer and store, acceptable to the target patient population, delivers the correct dosage, and has the desired effect when administered. To do so, it is important to select the correct chemical and physical forms of a drug at an early stage in development, as formulation changes can be very costly, create delays and result in poor quality clinical data that is difficult to interpret.
Dr Elizabeth Vadas describes the challenges of drug formulation and explains how and why she has been assisting the project teams at MMV.
1. What formulation challenges do drug developers face?
Poor solubility, low permeability and, in particular, lack of potency represent significant formulation challenges. For example, the formulation of low potency drugs, requiring high doses, is technically complex, especially in the field of malaria where we deal with combination drugs – two different molecules in one capsule or tablet. If, for example, the dose of one or both drugs is high, the tablet may become too large to swallow. We must then divide the dose into several smaller tablets.
2. Are there any other challenges particular to malaria drug development?
Yes, since the target population for malaria drugs is mainly sick children, we must formulate for them. Specific considerations for children include dosage form, ease of administration and palatability – bearing in mind the patient is likely to already be nauseous. Working with drug combinations complicates formulation further as the two active entities must be chemically compatible; if not, we need to come up with formulation approaches that can separate the two active ingredients in one dosage form. This can be a high technical hurdle. The stability of the dosage form in hot and humid countries represents an additional challenge.
Ideally, we would like to achieve all this in a single-dose cure – a goal which increases the scientific and technical complexity both for the drug molecule and the formulation.
3. What motivates you to work with MMV on a pro bono basis and how have you helped the project teams to overcome formulation challenges?
I have had a wonderful, productive career in the pharmaceutical industry, and now that I am retired I feel it is time to give something back. I hope that I have been able to advise the MMV teams on potency, form selection and other formulation requirements before molecules enter phase I trials. Together, we have been able to find promising formulation approaches for MMV048 and DSM265. The more issues we solve at the beginning of drug development the more likely we are to succeed.