Concomitant polymorphs

Joel Bernstein, Roger J. Davey, Jan Olav Henck

Research output: Contribution to journalReview articlepeer-review

734 Scopus citations

Abstract

Chemists who encounter polymorphism for the first time are often unaware of its existence and baffled by its manifestations. Experimental problems might include, for example, variable or diffuse melting point, crystal batches with inconsistent physical properties (electrical or thermal conductivity, filtering, drying, flow, tabletting, dissolution), or two (or more) different colored or different shaped crystals in the same batch of (chemically) 'pure' material. These problems arise because the conditions of the particular crystallization have led to the production of a number of polymorphs, which are present in the crystallizing medium or vessel at the time the crystals are harvested. The fact that polymorphs of a substance can appear concomitantly has long been recognized but rarely noted or studied. Is the phenomenon of concomitant polymorphs a curse or a blessing? It can be both. It is a curse for the chemist seeking a pure substance and a robust procedure to repeatedly and consistently produce the pure material, and the existence of concomitant polymorphs corrupts that procedure. It is a blessing, however, because (the recognition of) the existence of polymorphs in general, and concomitant polymorphs in particular, can provide the information and the opportunity to gain control over the crystallization process, and to achieve the desired specificity and robustness. An understanding of the competing thermodynamic and kinetic factors that govern the crystallization of polymorphs in general, or of a particular substance in particular, facilitates the control over the production of the desired polymorph, to the exclusion of undesired ones. Such control has important implications in a variety of industrial applications, of which pharmaceutical production and formulation is but one important example. This review covers the factors that govern competitive polymorphic crystallization and the rationale behind concomitantly crystallizing polymorphs, followed by a survey of concomitant polymorphs of a variety of chemical systems and a variety of crystallization procedures and conditions.

Original languageEnglish
Pages (from-to)3440-3461
Number of pages22
JournalAngewandte Chemie - International Edition
Volume38
Issue number23
DOIs
StatePublished - 3 Dec 1999

Keywords

  • Concomitant polymorphs
  • Crystallization kinetics polymorphism
  • Thermodynamics

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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