Effect of Rapid Pressurization on the Solubility of Small Organic Molecules

Crystallization under high pressure is an attractive approach to generate novel crystal polymorphs, solvates, and co-crystals of pharmaceuticals and other specialty chemicals. Here, we describe the effect of pressurization on the solubility of two common crystallization standards, paracetamol and piracetam. Simple theoretical models were developed to predict the change in solubility both due to pressurization and due to the temperature increase associated with adiabatic compression of the solution. These models were validated experimentally and provide a basis for experimental design. Interestingly, the decrease in solubility due to pressurization is often balanced by the increase in solubility from the temperature increase due to adiabatic compression of the solution.