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

ABSTRACTThe 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