General principles of pharmaceutical solid polymorphism: A supramolecular perspective

  • Rodríguez-Spong B
  • Price C
  • Jayasankar A
 et al. 
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Abstract

The diversity of solid-state forms that an active pharmaceutical ingredient (API) may attain relies on the repertoire of non-covalent interactions and molecular assemblies, the range of order, and the balance between entropy and enthalpy that defines the free energy landscape. It is recognized that crystallization is associated with molecular recognition events that lead to self-assembly, and that pharmaceutical function and thermodynamic stability can be altered with a slight change in the interacting molecules or their molecular network motifs. Our current understanding of pharmaceutical solids in terms of molecular recognition and complementarity provides new insights into the design and function of single and fully miscible, multiple-component solids with varying degrees of order, from amorphous to crystalline states, and in this way is leading the path to supramolecular pharmaceutics. This review describes pharmaceutical solids in terms of supramolecular chemistry and crystal engineering concepts, and discusses the events that control crystallization and solid phase transformations. © 2003 Elsevier B.V. All rights reserved.

Author-supplied keywords

  • Cocrystals
  • Crystal engineering
  • Crystallization
  • Molecular dispersions
  • Solvates
  • Supramolecular isomers
  • Supramolecular pharmaceutics

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Authors

  • Barbara Rodríguez-Spong

  • Christopher P. Price

  • Adivaraha Jayasankar

  • Adam J. Matzger

  • Naír Rodríguez-Hornedo

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