(56b) Computational Support of Solid Form Selection in Pharmaceutical Industry

In the pharmaceutical industry, drug polymorphism can be a critical problem, and is the subject of various regulatory considerations. One of the principal concerns is based on an effect that polymorphism may have on a drug’s bioavailability due to change of its solubility and dissolution rate. Therefore, in Pharmaceutical industry, it is quite crucial to get comprehensive information on the available drug polymorphs and their relative stability and solubility.

State-of-the art computational approaches were proposed and developed to support the commercial solid state nomination. Rational solvent selection is adopted to guide polymorph screening experiments. In addition, computational methods enable an estimation of the likelihood of existence of an unknown, more stable form of the drug, as well as its potential impact on drug’s solubility (and bioavailability). These computational methods involve crystal structure prediction, prediction of drug solubility and conformer distribution in organic solvents and solvent mixtures, in silico hydrogen bonding propensity estimation. A detailed application of these computational tools in the pharmaceutical industry is illustrated on a selective dual ALK and c-MET inhibitor crizotinib (trade name Xalkori) and on a VEGF inhibitor axitinib (trade name Inlyta).