Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and Safety
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 meth...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/10/1600 |
| _version_ | 1797513431162552320 |
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| author | Katarzyna Regulska Joanna Musiał Beata J. Stanisz |
| author_facet | Katarzyna Regulska Joanna Musiał Beata J. Stanisz |
| author_sort | Katarzyna Regulska |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T06:16:29Z |
| format | Article |
| id | doaj.art-abd8748878b541e0bf5c5e7b71267e6a |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T06:16:29Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-abd8748878b541e0bf5c5e7b71267e6a2023-11-22T19:38:18ZengMDPI AGPharmaceutics1999-49232021-10-011310160010.3390/pharmaceutics13101600Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and SafetyKatarzyna Regulska0Joanna Musiał1Beata J. Stanisz2Greater Poland Cancer Center, 15th Garbary Street, 61-866 Poznan, PolandDepartment of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka Street, 60-780 Poznan, PolandDepartment of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka Street, 60-780 Poznan, PolandHigh 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.https://www.mdpi.com/1999-4923/13/10/1600ramiprilstability in solid stateexcipientstabletsdegradation impurities |
| spellingShingle | Katarzyna Regulska Joanna Musiał Beata J. Stanisz Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and Safety Pharmaceutics ramipril stability in solid state excipients tablets degradation impurities |
| title | Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and Safety |
| title_full | Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and Safety |
| title_fullStr | Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and Safety |
| title_full_unstemmed | Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and Safety |
| title_short | Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and Safety |
| title_sort | solid state stability profiling of ramipril to optimize its quality efficiency and safety |
| topic | ramipril stability in solid state excipients tablets degradation impurities |
| url | https://www.mdpi.com/1999-4923/13/10/1600 |
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