Methods for Polymorphic Screening
Many chemical compounds can exist in multiple crystalline forms, which are called polymorphs. Polymorphs have the same composition, but their properties can vary markedly. In many fields, conditions for crystallization are screened exhaustively to generate as many polymorphs as possible, from which the most advantageous form can be selected. In the pharmaceutical industry, for example, the most desirable polymorphs may be those with the highest solubility in water (to maximize bioavailability), the greatest thermodynamic stability (to ensure that conversion into a more stable form cannot occur), or a tendency to crystallize in particular shapes (to facilitate handling or formulation). When a previously unknown polymorph is discovered and found to have superior properties, it can be patented as a new form of matter. We have devised new ways to screen for polymorphs, using techniques we call mixed-crystal seeding and suspended-melt crystallization. In new work, we will further explore the scope of these methods, define the best ways to employ them, and use them to screen for new polymorphs of pharmaceutically active compounds of particular interest to adMare.