Insight into the phase changes of pharmaceutical salts during processing

Nowadays more and more new drug candidates are poorly water soluble due to the increased size
and lipophilicity of the candidate molecules. The low solubility of the drugs limit their bioavailability.
Therefore, there is a growing interest in the pharmaceutical industry to techniques that can be used to
improve the solubility of drugs. One effective way to increase the aqueous solubility of a drug substance is salt formation. However, during processing a salt can be very unstable, it may transform to free acid/base, it may also convert to amorphous matter, and other polymorphs or solvates. The situation can be even more complex when considering typical formulation with different types of excipients present in the final dosage form. An effective control of the chemical and physical stability of salt API in the formulation during processing can thus be expected to be critical to the final product quality. So far the fundamental research to understand these phase transitions is limited. This post-doctoral work is aiming at understanding the underlying fundamental and mechanism of the phase transformation between the solid forms of salts during processing and storage. The fundamental knowledge gained in this project about the behavior of salts will be useful to the pharmaceutical industry.