Version 1
: Received: 1 May 2024 / Approved: 2 May 2024 / Online: 7 May 2024 (03:15:03 CEST)
How to cite:
Hou, J.; Zhao, P.; Wang, Y.; Jiang, X.; Fu, Q. Co-amorphization of Acemetacin with Basic Amino Acids as Co-formers for Solubility Improvement and Side Effect Mitigation. Preprints2024, 2024050123. https://doi.org/10.20944/preprints202405.0123.v1
Hou, J.; Zhao, P.; Wang, Y.; Jiang, X.; Fu, Q. Co-amorphization of Acemetacin with Basic Amino Acids as Co-formers for Solubility Improvement and Side Effect Mitigation. Preprints 2024, 2024050123. https://doi.org/10.20944/preprints202405.0123.v1
Hou, J.; Zhao, P.; Wang, Y.; Jiang, X.; Fu, Q. Co-amorphization of Acemetacin with Basic Amino Acids as Co-formers for Solubility Improvement and Side Effect Mitigation. Preprints2024, 2024050123. https://doi.org/10.20944/preprints202405.0123.v1
APA Style
Hou, J., Zhao, P., Wang, Y., Jiang, X., & Fu, Q. (2024). Co-amorphization of Acemetacin with Basic Amino Acids as Co-formers for Solubility Improvement and Side Effect Mitigation. Preprints. https://doi.org/10.20944/preprints202405.0123.v1
Chicago/Turabian Style
Hou, J., Xiwei Jiang and Qiang Fu. 2024 "Co-amorphization of Acemetacin with Basic Amino Acids as Co-formers for Solubility Improvement and Side Effect Mitigation" Preprints. https://doi.org/10.20944/preprints202405.0123.v1
Abstract
Acemetacin (ACM) is a new non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. However, the poor water solubility and gastrointestinal side effects limit its use. Recently, the co-amorphous (CAM) strategy has attracted great interest to improve solubility for poorly water-soluble drugs, and basic amino acids have the potential to protect the gastrointestinal tract. In order to develop highly efficient and low toxic ACM formulation, we propose to prepare ACM CAM, with basic amino acids (lysine, arginine and histidine) as co-formers, using a cryo-milling method. The solid-state behaviors of the ACM CAMs were characterized by polarizing light microscopy, differential scanning calorimetry and powder X-ray diffraction. Fourier transform infrared spectroscopy and molecular docking were carried out to understand the formation mechanism. Moreover, the gastro-protective effects of ACM CAMs were evaluated in a rat gastric ulcer model. The results demonstrated CAMs improved the dissolution rates of ACM compared with the neat amorphous counterpart. Furthermore, ACM CAMs are significantly effective in mitigating the ACM-induced gastric ulcer in rats, and the ulcer inhibition rates were almost 90%. More importantly, this study provided a useful method for mitigating drug-induced gastrointestinal damage and broadened the applications of drug-amino acid CAMs.
Copyright:
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