Research Paper

Pharmaceutical Research

, Volume 29, Issue 10, pp 2777-2791

First online:

Stabilization of a Supersaturated Solution of Mefenamic Acid from a Solid Dispersion with EUDRAGIT® EPO

  • Taro KojimaAffiliated withChiba University
  • , Kenjirou HigashiAffiliated withChiba University
  • , Toyofumi SuzukiAffiliated withChiba University
  • , Kazuo TomonoAffiliated withChiba University
  • , Kunikazu MoribeAffiliated withChiba University
  • , Keiji YamamotoAffiliated withChiba University Email author 

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The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT® EPO (EPO) was investigated.


The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions.


Dissolution tests in acetate buffer (pH 5.5) revealed that solid dispersion showed > 200-fold higher concentration of MFA. Supersaturated solution was stable over 1 month and exhibited improved oral bioavailability of MFA in rats, with a 7.8-fold higher area under the plasma concentration-versus-time curve. Solid-state 1H spin–lattice relaxation time (T1) measurement showed that MFA was almost monomolecularly dispersed in the EPO polymer matrix. Intermolecular interaction between MFA and EPO was indicated by solid-state infrared and 13C-T1 measurements. Solution-state 1H-NMR measurement demonstrated that MFA existed in monomolecular state in supersaturated solution. 1H-T1 and difference nuclear Overhauser effect measurements indicated that cross relaxation occurred between MFA and EPO due to the small distance between them.


The formation and high stability of the supersaturated solution were attributable to the specifically formed intermolecular interactions between MFA and EPO.

Key words

solid dispersion supersaturation NMR oral bioavailability EUDRAGIT® EPO