دورية أكاديمية
Dual Functionality of Poloxamer 188 in Freeze-Dried Protein Formulations: A Stabilizer in Frozen Solutions and a Bulking Agent in Lyophiles.
| العنوان: | Dual Functionality of Poloxamer 188 in Freeze-Dried Protein Formulations: A Stabilizer in Frozen Solutions and a Bulking Agent in Lyophiles. |
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| المؤلفون: | Li J; Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States., Munjal B; Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States., Zeng C; Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States., Suryanarayanan R; Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States. |
| المصدر: | Molecular pharmaceutics [Mol Pharm] 2024 May 06; Vol. 21 (5), pp. 2555-2564. Date of Electronic Publication: 2024 Mar 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101197791 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1543-8392 (Electronic) Linking ISSN: 15438384 NLM ISO Abbreviation: Mol Pharm Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, c2004- |
| مواضيع طبية MeSH: | Freeze Drying*/methods , Poloxamer*/chemistry , Excipients*/chemistry , Trehalose*/chemistry , Calorimetry, Differential Scanning*/methods, Sucrose/chemistry ; X-Ray Diffraction ; L-Lactate Dehydrogenase/metabolism ; L-Lactate Dehydrogenase/chemistry ; Crystallization/methods ; Chemistry, Pharmaceutical/methods ; Proteins/chemistry ; Drug Compounding/methods ; Freezing |
| مستخلص: | Poloxamer 188 (P188) was hypothesized to be a dual functional excipient, (i) a stabilizer in frozen solution to prevent ice-surface-induced protein destabilization and (ii) a bulking agent to provide elegant lyophiles. Based on X-ray diffractometry and differential scanning calorimetry, sucrose, in a concentration-dependent manner, inhibited P188 crystallization during freeze-drying, while trehalose had no such effect. The recovery of lactate dehydrogenase (LDH), the model protein, was evaluated after reconstitution. While low LDH recovery (∼60%) was observed in the lyophiles prepared with P188, the addition of sugar improved the activity recovery to >85%. The secondary structure of LDH in the freeze-dried samples was assessed using infrared spectroscopy, and only moderate structural changes were observed in the lyophiles formulated with P188 and sugar. Thus, P188 can be a promising dual functional excipient in freeze-dried protein formulations. However, P188 alone does not function as a lyoprotectant and needs to be used in combination with a sugar. |
| فهرسة مساهمة: | Keywords: X-ray diffractometry; conformational stability; differential scanning calorimetry; freeze-drying; lactate dehydrogenase; poloxamer; protein activity; protein formulation; surfactant |
| المشرفين على المادة: | 106392-12-5 (Poloxamer) 0 (Excipients) B8WCK70T7I (Trehalose) 57-50-1 (Sucrose) EC 1.1.1.27 (L-Lactate Dehydrogenase) 0 (Proteins) |
| تواريخ الأحداث: | Date Created: 20240329 Date Completed: 20240506 Latest Revision: 20240506 |
| رمز التحديث: | 20240506 |
| DOI: | 10.1021/acs.molpharmaceut.4c00108 |
| PMID: | 38551918 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1543-8392 |
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| DOI: | 10.1021/acs.molpharmaceut.4c00108 |