Polymorphism in active pharmaceutical ingredients (APIs) plays a crucial role both for medical and intellectual property concerns but despite ongoing efforts, experimental and computational investigations of the existence and the physical-chemical properties of the same compound in different forms is still an open question. Quantum mechanical computational methods describe the systems at 0K, but experimentally properties are often evaluated at room temperature. Therefore it is not surprising that results determined from first principles dramatically differ from those obtained experimentally. By applying a quantum mechanical periodic approach that takes into account long range dispersion forces fitted for solid materials, and by imposing different cell volumes corresponding to different thermodynamic conditions, we show how results from calculations at 0K may be compared to experimental values at higher temperatures. Where experimental results are not available, our work represents an innovative approach in addressing the properties of APIs.

Active pharmaceutical ingredients: Prediction of physical-chemical properties from first principles

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.