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Additive-Induced Metastable Single Crystal of Mefenamic Acid

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Purpose

To utilize additives to develop a strategy and a method to grow single crystals that allow structure determination of a metastable form of a drug.

Materials and Methods

The metastable form of mefenamic acid (MFA) was grown in the presence of various amounts of the structurally similar additive flufenamic acid (FFA) in ethanol. Single crystal X-ray analysis was performed on the single crystals of MFA II that were formed. The solubility of MFA in the presence of FFA was measured to elucidate the mechanism of MFA II formation.

Results

A supersaturated solution of MFA in ethanol produced the metastable form using FFA as an additive. Ethanol–water mixtures and toluene were also used to investigate the relationships between form produced and solvent since these two solvent systems do not produce MFA II.

Conclusions

Additives can be used to obtain the metastable form of pharmaceutical compounds, and the relationships between molecules and solvent as well as between host and guest molecules are critical to obtaining the desired form.

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Acknowledgments

Eun Hee Lee thanks Dr. Phillip E. Fanwick for crystal structure solution of MFA II. The financially support from the Purdue-Michigan Program on the Chemical and Physical Stability of Pharmaceutical Solids is acknowledged.

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Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA

    Eun Hee Lee, Stephen R. Byrn & M. Teresa Carvajal

Authors
  1. Eun Hee Lee
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  2. Stephen R. Byrn
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  3. M. Teresa Carvajal
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Correspondence to Stephen R. Byrn.

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Lee, E.H., Byrn, S.R. & Carvajal, M.T. Additive-Induced Metastable Single Crystal of Mefenamic Acid. Pharm Res 23, 2375–2380 (2006). https://doi.org/10.1007/s11095-006-9045-y

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  • DOI: https://doi.org/10.1007/s11095-006-9045-y

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