Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and Safety

Pharmaceutics

Joanna Musiał¹  Beata J. Stanisz¹  Katarzyna Regulska² 

[1] Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka Street, 60-780 Poznan, Poland;Greater Poland Cancer Center, 15th Garbary Street, 61-866 Poznan, Poland;

关键词: ramipril;    stability in solid state;    excipients;    tablets;    degradation impurities;   

DOI  :  10.3390/pharmaceutics13101600

来源: DOAJ

【 摘 要 】

High global expenditure on out-of-label-date drugs, along with safety concerns associated with the accumulation of degradation impurities, justify the need for stability profiling. In this article, a comprehensive study on the solid-state stability of ramipril (RAM) was performed via isothermal methods under stress conditions. A validated stability-indicating HPLC protocol was used. The effects of various factors on the rate of RAM degradation were investigated, including: temperature, relative air humidity (RH), excipients (talc, starch, methylcellulose and hydroxypropyl methylcellulose), mode of tablet storage, and immediate packaging. The degradation impurities were also identified by HPLC–MS. It was found that RAM was unstable, and temperature accelerated its degradation. RAM was also vulnerable to RH changes, suggesting that it must be protected from moisture. The reaction followed first-order kinetics. The studied excipients stabilized RAM as a pure substance. The tableting process deteriorated its stability, explaining the need for appropriate immediate packaging. RAM in the form of tablets must be stored in blisters, and it cannot be crushed into two halves. The degradation impurities were ramiprilat and the diketopiperazine derivative.

【 授权许可】

Unknown