Preparation and characterization of glimepiride eutectic mixture with L-arginine for improvement of dissolution rate

Heejun Park, Hye Jin Seo, Eun Sol Ha, Seung hyeon Hong, Jeong Soo Kim, Min Soo Kim, Sung Joo Hwang

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11 Citations (Scopus)


In this study, glimepiride and L-arginine (GA) binary mixtures at various molar ratios were prepared to evaluate whether they could improve the poor water solubility and dissolution characteristics of glimepiride. It was shown that glimepiride and arginine form a eutectic mixture, a type of crystalline solid dispersions, at a 1:1 M ratio and eutectic temperature of 426.9 K using a phase diagram constructed using differential scanning calorimetry (DSC) and thermo-microscopy. The preserved characteristic powder X-ray diffraction (PXRD) patterns and infrared (IR) spectra of each material in those of GA binary mixtures confirmed the formation of eutectic mixture without molecular interaction in solid state. The formation of GA eutectic mixture (GAEM) resulted in the improvement of solubility through pH modification and the intermolecular interaction of glimepiride and L-arginine in aqueous mediums, thereby wettability and dissolution rate of glimepiride were also enhanced. The intermolecular interaction between glimepiride and L-arginine at a 1:1 stoichiometry of the complex in solution state was identified by phase solubility, stoichiometric determination, and solution state nuclear magnetic resonance (NMR) spectroscopy. Specific molecular interactions such as hydrogen bonding and hydrophobic interaction were suggested as main mechanisms of GA complexation in solution. Therefore, this study concludes that the GAEM could be an effective way to improve the solubility and dissolution rate of glimepiride.

Original languageEnglish
Article number119288
JournalInternational Journal of Pharmaceutics
Publication statusPublished - 2020 May 15

Bibliographical note

Funding Information:
This study was supported by a grant from Basic Science Research Program ( NRF-2019R1F1A1056350 ), and Key Research Institutes in Universities ( NRF-2018R1A6A1A03023718 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT & Future Planning, Republic of Korea .

Publisher Copyright:
© 2020 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


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