Stabilization of Metastable Flufenamic Acid by Inclusion of Mefenamic Acid: Solid Solution or Epilayer?

• Published in: Journal of pharmaceutical sciences Vol. 99; no. 9; pp. 4013 - 4022
• Main Authors: Lee, Eun Hee, Byrn, Stephen R.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.09.2010; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Anti-Inflammatory Agents - chemistry; Biological and medical sciences; Crystallization; Drug Stability; epilayer; flufenamic acid; Flufenamic Acid - chemistry; General pharmacology; inclusion compound; Medical sciences; mefenamic acid; Mefenamic Acid - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powder Diffraction; solid solution; solid-state polymorphic transformation; Solubility; X-Ray Diffraction; inclusion compound; flufenamic acid; solid solution; mefenamic acid; epilayer; solid-state polymorphic transformation; Prostaglandin-endoperoxide synthase; Pharmaceutical technology; Enzyme; Stabilization; Fenamic acid derivatives; Enzyme inhibitor; Flufenamic acid; Polymorphic transformation; Non steroidal antiinflammatory agent; Solid state; Analgesic; Mefenamic acid; Antipyretic; Anthranilic acid derivatives; Oxidoreductases; Inclusion compound; Solution
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.22250

The physical stability of metastable form I of flufenamic acid (FFA) increased by using mefenamic acid (MFA) as an inclusion compound. We studied the extent of this effect and explained the mechanism by investigating the effect of the presence of MFA on nucleation and crystal growth of the mixed crystals and the effects it has on the surface morphology. We conclude that the polymorphic transformation of FFA was inhibited in the presence of MFA both by lowering the difference in free energy of the MFA/FFA I and MFA/FFA III solid solution crystals, and also by forming an epilayer, thus affecting the kinetics of the polymorphic transformation. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4013–4022, 2010