Co-amorphization of atorvastatin by lisinopril as a co-former for solubility improvement.

Abstract

The co-amorphous (CAM) technology has attracted extensive attention in recent years because it can improve the solubility and provide a formulation strategy for fixed dose combination for poorly water-soluble drugs. Atorvastatin (ATR) is a poorly water-soluble drug and it has strong anti-hyperlipidemia activity, and it is usually used in combination with lisinopril (LNP), an anti-hypertension drug. The aim of this study is to test the feasibility to develop ATR/LNP co-amorphous formulation using a cryo-milling method. The solid-state behaviors of the CAM systems were characterized by polarizing light microscopy, differential scanning calorimetry and powder X-ray diffraction. The molecular interaction between ATR and LNP was confirmed by the analysis of glass transition temperature and Fourier transform infrared spectroscopy. Compared with crystalline ATR and neat amorphous ATR, the CAM systems showed significantly increased in vitro dissolution and intrinsic dissolution rate of ATR, because LNP enhanced the supersaturation maintenance of ATR and inhibited its solution-mediated recrystallization to a certain extent.

• Authors: Wen Li, Jiaqi Song, Jianfeng Li, Mo Li, Baocheng Tian, Zhonggui He, Xiaohong Liu, Qiang Fu
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 607 Pg. 120971 (Sep 25 2021) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 34363915 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Atorvastatin
• Lisinopril

Topics

• Atorvastatin
• Calorimetry, Differential Scanning
• Drug Compounding
• Drug Stability
• Lisinopril
• Solubility
• Spectroscopy, Fourier Transform Infrared
• X-Ray Diffraction