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Pharmaceutical Research

, Volume 19, Issue 7, pp 1013–1018 | Cite as

Characterization of Mefenamic Acid-Guaiacol Ester: Stability and Transport Across Caco-2 Cell Monolayers

  • Vimon TantishaiyakulEmail author
  • Kamonthip Wiwattanawongsa
  • Sirirat Pinsuwan
  • Srirat Kasiwong
  • Narubodee Phadoongsombut
  • Sanae Kaewnopparat
  • Nattha Kaewnopparat
  • Yon Rojanasakul
Article

Abstract

Purpose. Prodrug of non-steroidal anti-inflammatory drugs (NSAIDs) or NSAIDs linked with guaiacol have been reported to suppress gastrointestinal (GI) toxicity or induce GI protective effect. In this study, mefenamic-guaiacol ester was synthesized and its physicochemical properties, stability, and transport across Caco-2 monolayers were investigated.

Methods. Synthesis of the ester was carried out using mefenamic acid, guaiacol, N, N′-dimethylaminopyridine, and N, N′dicyclohexylcarbodiimide. The hydrolysis of the ester was investigated in aqueous buffer solutions pH 1-12 as well as in Caco-2 homogenate, human plasma, and porcine liver esterase. Caco-2 cell monolayers were utilized for transport studies. Due to the high lipophilicity of the ester with a calculated logP of 6.15, bovine serum albumin (BSA, 4%) was included in the receiver compartment to obtain a good in vitro-in vivo correlation. Permeation of the ester was assessed with or without the exposure of cells to PMSF, an inhibitor of esterase.

Results. The ester was stable at a wide pH range from 1-10. However, it was hydrolyzed by enzymes from porcine liver esterase and Caco-2 homogenate. With the PMSF exposure on the apical (AP) side and in the presence of 4% BSA on the basolateral (BL) side, the transported amount of the ester from AP-to-BL direction was 14.63% after 3 hr with a lag time of 23 min. The Papp for the ester was 4.72 × 10-6 cm s-1.

Conclusion. The results from hydrolysis studies indicate that this ester is a prodrug. The Papp value suggests the moderate absorption characteristic of the compound. The accumulation of this highly lipophilic ester in Caco-2 cells is reduced in the presence of BSA.

mefenamic acid guaiacol prodrug caco-2 cells hydrolysis transport 

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Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Vimon Tantishaiyakul
    • 1
    Email author
  • Kamonthip Wiwattanawongsa
    • 1
  • Sirirat Pinsuwan
    • 2
  • Srirat Kasiwong
    • 1
  • Narubodee Phadoongsombut
    • 1
  • Sanae Kaewnopparat
    • 2
  • Nattha Kaewnopparat
    • 2
  • Yon Rojanasakul
    • 3
  1. 1.Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical SciencesPrince of Songkla UniversityHat-Yai, SongkhlaThailand
  2. 2.Department of Pharmaceutical Technology, Faculty of Pharmaceutical SciencesPrince of Songkla UniversityHat-Yai, SongkhlaThailand
  3. 3.Department of Basic Pharmaceutical Sciences, School of PharmacyWest Virginia UniversityMorgantown

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