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Accessing Mefenamic Acid Form II through High-Pressure Recrystallisation.

Nasir Abbas1, Iain D H Oswald2, Colin R Pulham3

  • 1College of Pharmacy, University of the Punjab, Lahore 54000, Pakistan. nasirabbas77@gmail.com.

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Summary

High-pressure crystallization successfully prepared a new form of mefenamic acid (MA). Mefenamic acid

Keywords:
diamond anvil cellhigh-pressurehigh-pressure crystallisationmefenamic acidnon-steroidal anti-inflammatory drugspolymorphism

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Area of Science:

  • Solid-state chemistry
  • Materials science
  • Crystallography

Background:

  • Mefenamic acid (MA) is a non-steroidal anti-inflammatory drug.
  • Understanding its polymorphic forms is crucial for drug formulation and efficacy.
  • Previous studies have not explored high-pressure crystallization for MA polymorphs.

Purpose of the Study:

  • To investigate high-pressure crystallization as a novel method for preparing mefenamic acid (MA) polymorphs.
  • To characterize the crystal structure of the high-pressure form.
  • To study the mechanical response of mefenamic acid (MA) Form I under pressure.

Main Methods:

  • High-pressure crystallization using a diamond anvil cell.
  • Single-crystal X-ray diffraction.
  • Unit cell volume compression studies.

Main Results:

  • Successfully prepared a novel Form II of mefenamic acid (MA) via high-pressure crystallization at 0.3 GPa.
  • The high-pressure Form II exhibits efficient molecular packing attributed to MA's structural flexibility.
  • Mefenamic acid (MA) Form I showed a 14% unit cell volume decrease up to 2.5 GPa without phase transition.

Conclusions:

  • High-pressure crystallization is an effective alternative method for obtaining specific mefenamic acid (MA) polymorphs.
  • The structural flexibility of mefenamic acid (MA) plays a key role in its crystal packing under pressure.
  • Reconstructive phase transitions, induced by high pressure, are necessary for significant conformational changes in mefenamic acid (MA).