Polymorph control is of key importance in the synthesis of drug substances, as individual polymorphs can exhibit differences in solubility and stability. This can have an impact on drug efficacy and bioavailability. Where this is the case, regulators require that acceptance criteria are established.
We have used solubility studies and thermal stability investigations to gain greater understanding of the recrystallisation process and the polymorphic landscape. The solubility curve and the meta-stable zone have been plotted, and verification experiments performed. We have used this information to improve the final isolation procedure for a potential drug substance, allowing consistent production of a more thermally-stable polymorph than was obtained from the original procedure.
We concluded by performing physical characterisation work on this polymorph, using a range of instruments to benchmark its stability to both temperature and humidity.
