Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations
Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability. However, some excipients are prone to degradation during repeated use and/or improper storage, and the impurities generated by their degradation are easily overlooked by end users and are usually not...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Journal of Pharmaceutical Analysis |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177922000211 |
| _version_ | 1811336088829034496 |
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| author | Min-Fei Sun Jia-Ning Liao Zhen-Yi Jing Han Gao Bin-Bin Shen You-Fu Xu Wei-Jie Fang |
| author_facet | Min-Fei Sun Jia-Ning Liao Zhen-Yi Jing Han Gao Bin-Bin Shen You-Fu Xu Wei-Jie Fang |
| author_sort | Min-Fei Sun |
| collection | DOAJ |
| description | Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability. However, some excipients are prone to degradation during repeated use and/or improper storage, and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored, affecting the stability of biopharmaceuticals. In this study, we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry (GC-MS). The other polyol excipient, mannitol, was much more stable than glycerol. The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide, thymopentin, were also evaluated. The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol, compared to 95.8% in other formulations after the stress test. Most glycerol impurities (i.e., aldehydes and ketones) reacted with thymopentin, affecting the stability of thymopentin formulations. In conclusion, this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage. Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results. |
| first_indexed | 2024-04-13T17:34:25Z |
| format | Article |
| id | doaj.art-9294e34f33474a0faa3bc12f7df4cb69 |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-04-13T17:34:25Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-9294e34f33474a0faa3bc12f7df4cb692022-12-22T02:37:28ZengElsevierJournal of Pharmaceutical Analysis2095-17792022-10-01125774782Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulationsMin-Fei Sun0Jia-Ning Liao1Zhen-Yi Jing2Han Gao3Bin-Bin Shen4You-Fu Xu5Wei-Jie Fang6Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou Biopharm Town, Hangzhou, 310016, ChinaInstitute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, ChinaInstitute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, ChinaInstitute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou Biopharm Town, Hangzhou, 310016, ChinaInstitute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou Biopharm Town, Hangzhou, 310016, ChinaZhejiang Haisheng Pharmaceutical Inc., Taizhou, Zhejiang, 318000, ChinaInstitute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou Biopharm Town, Hangzhou, 310016, China; Corresponding author. Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability. However, some excipients are prone to degradation during repeated use and/or improper storage, and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored, affecting the stability of biopharmaceuticals. In this study, we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry (GC-MS). The other polyol excipient, mannitol, was much more stable than glycerol. The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide, thymopentin, were also evaluated. The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol, compared to 95.8% in other formulations after the stress test. Most glycerol impurities (i.e., aldehydes and ketones) reacted with thymopentin, affecting the stability of thymopentin formulations. In conclusion, this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage. Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.http://www.sciencedirect.com/science/article/pii/S2095177922000211Excipient stabilityGC-MSGlycerolLC-MS/MSMannitolThymopentin |
| spellingShingle | Min-Fei Sun Jia-Ning Liao Zhen-Yi Jing Han Gao Bin-Bin Shen You-Fu Xu Wei-Jie Fang Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations Journal of Pharmaceutical Analysis Excipient stability GC-MS Glycerol LC-MS/MS Mannitol Thymopentin |
| title | Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations |
| title_full | Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations |
| title_fullStr | Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations |
| title_full_unstemmed | Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations |
| title_short | Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations |
| title_sort | effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations |
| topic | Excipient stability GC-MS Glycerol LC-MS/MS Mannitol Thymopentin |
| url | http://www.sciencedirect.com/science/article/pii/S2095177922000211 |
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