Pharmaceutical Research

, Volume 29, Issue 10, pp 2777–2791 | Cite as

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

  • Taro Kojima
  • Kenjirou Higashi
  • Toyofumi Suzuki
  • Kazuo Tomono
  • Kunikazu Moribe
  • Keiji Yamamoto
Research Paper

Abstract

Purpose

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

Methods

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.

Results

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.

Conclusions

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 

Supplementary material

11095_2011_655_MOESM1_ESM.doc (212 kb)
Esm 1(DOC 212 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Taro Kojima
    • 1
  • Kenjirou Higashi
    • 1
  • Toyofumi Suzuki
    • 1
  • Kazuo Tomono
    • 1
  • Kunikazu Moribe
    • 1
  • Keiji Yamamoto
    • 1
  1. 1.Chiba UniversityChibaJapan

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