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Keywords:

  • in silico modeling;
  • glass transition;
  • hierarchical cluster analysis;
  • mathematical model;
  • multivariate analysis;
  • computer-aided drug design

Abstract

It is well known that the amorphous state can greatly enhance the bioavailability of drugs. However, comparatively few compounds form either liquids at room temperature or glasses above it. We present qualitative insights as to why some molecules would form glasses instead of crystals and a fast, straightforward, physically well founded, and nonproprietary method to calculate the expected glass transition temperature before the synthesis of a new drug. This way, a selection of drug candidates can be screened for one that has a high tendency to vitrify and a preferably low temperature of this transition. The new method works reliably for a great span of possible molecules, encompassing well-known drugs, nutrients, and a multitude of other technically interesting compounds. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1970–1980, 2013