Stabilization of a metastable polymorph of sulfamerazine by structurally related additives

Chong Hui Gu, Koustuv Chatterjee, Victor G Young, David J.W. Grant

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The influence of structurally related additives, namely N4-acetylsulfamerazine (NSMZ), sulfadiazine (SD) or sulfamethazine (SM), on the rate of the solvent-mediated polymorphic transformation (I→II) of sulfamerazine in acetonitrile (ACN) at 24°C was studied. The transformation rate is controlled by the crystallization rate of the more stable Polymorph II. All three impurities exhibit inhibitory effects on the crystallization of Polymorph II and hence stabilize the metastable Polymorph I in ACN suspension. The rank order of the inhibitory effect (NSMZ ≫ SD > SM) is the same as the rank order of the binding energy of the impurity molecule to the surface of the host crystal. The relationship between the concentration of the impurity and the inhibitory effect was fitted to various models and was found to be best described by a model based on the Langmuir adsorption isotherm.

Original languageEnglish (US)
Pages (from-to)471-481
Number of pages11
JournalJournal of Crystal Growth
Issue number1-4
StatePublished - Feb 2002

Bibliographical note

Funding Information:
We thank Bristol–Myers Squibb for an unrestricted grant and also the Supercomputing Institute of the University of Minnesota for financially supporting our use of the Medicinal Chemistry/Supercomputing Institute Visualization—Workstation Laboratory.


  • A1. Adsorption
  • A1. Computer simulation
  • A1. Crystal structure
  • A1. Impurities
  • A1. Nucleation
  • A2. Growth from solutions


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