Characterization and therapeutic efficacy evaluation of glimepiride and L-arginine co-amorphous formulation prepared by supercritical antisolvent process: Influence of molar ratio and preparation methods

Heejun Park, Hye Jin Seo, Seung hyeon Hong, Eun Sol Ha, Sibeum Lee, Jeong Soo Kim, In hwan Baek, Min Soo Kim, Sung Joo Hwang

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1 Citation (Scopus)

Abstract

The glimepiride/L-arginine (GA) binary systems were prepared at various molar ratios by using a supercritical antisolvent (SAS) process. For comparison, the GA system was also prepared by physical mixing (PM), melt quenching (MQ), and solvent evaporation (SE) methods. Analyses by DSC and PXRD showed that only the GA binary mixture at 1:1 M ratio prepared by the SAS process was a pure co-amorphous mixture with an excellent content uniformity. On the other hand, GA mixture prepared by PM and SE were not pure co-amorphous systems and contained crystalline eutectic mixture, and MQ method at 170 °C induced the decrease in drug content due to decomposition of glimepiride. The positive deviation of experimentally measured glass transition temperature (Tg) compared to predicted Tg by the Gordon Taylor equation suggests specific molecular interactions between glimepiride and L-arginine in solid-state GA co-amorphous (GACA) mixture. The intermolecular interactions between glimepiride and L-arginine in GACA system were characterized by FT-IR and solid-state NMR analyses. Improved glimepiride dissolution rate of GACA formulation were confirmed using the solubility test, contact angle measurement, and dissolution test. Furthermore, the evaluation of pharmacodynamic hypoglycemic effect demonstrated that GACA prepared by the SAS process significantly improved the therapeutic efficacy of glimepiride.

Original languageEnglish
Article number119232
JournalInternational Journal of Pharmaceutics
Volume581
DOIs
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 .

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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