دورية أكاديمية
In Situ Eutectic Formation in a Polymeric Matrix via Hot-Melt Reactive Extrusion and the Use of Partial Least Squares Regression Modeling for Reaction Yield Determination.
| العنوان: | In Situ Eutectic Formation in a Polymeric Matrix via Hot-Melt Reactive Extrusion and the Use of Partial Least Squares Regression Modeling for Reaction Yield Determination. |
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| المؤلفون: | Andrews GP; The Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, U.K., Culkin A; The Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, U.K., Jones DS; The Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, U.K., Li S; The Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, U.K. |
| المصدر: | Molecular pharmaceutics [Mol Pharm] 2024 Sep 02; Vol. 21 (9), pp. 4272-4284. Date of Electronic Publication: 2024 Aug 13. |
| نوع المنشور: | Journal Article |
| 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: | Polymers*/chemistry , Solubility*, Least-Squares Analysis ; Chemistry, Pharmaceutical/methods ; Maleates/chemistry ; Drug Compounding/methods ; Hot Temperature ; Hydrogen Bonding ; Hot Melt Extrusion Technology/methods ; Crystallization/methods |
| مستخلص: | There has been a significant volume of work investigating the design and synthesis of new crystalline multicomponent systems via examining complementary functional groups that can reliably interact through the formation of noncovalent bonds, such as hydrogen bonds (H-bonds). Crystalline multicomponent molecular adducts formed using this approach, such as cocrystals, salts, and eutectics, have emerged as drug product intermediates that can lead to effective drug property modifications. Recent advancement in the production for these multicomponent molecular adducts has moved from batch techniques that rely upon intensive solvent use to those that are solvent-free, continuous, and industry-ready, such as reactive extrusion. In this study, a novel eutectic system was found when processing albendazole and maleic acid at a 1:2 molar ratio and successfully prepared using mechanochemical methods including liquid-assisted grinding and hot-melt reactive extrusion. The produced eutectic was characterized to exhibit a 100 °C reduction in melting temperature and enhanced dissolution performance (>12-fold increase at 2 h point), when compared to the native drug compound. To remove handling of the eutectic as a formulation intermediate, an end-to-end continuous-manufacturing-ready process enables feeding of the raw parent reagents in their respective natural forms along with a chosen polymeric excipient, Eudragit EPO. The formation of the eutectic was confirmed to have taken place in situ in the presence of the polymer, with the reaction yield determined using a multivariate calibration model constructed by combining spectroscopic analysis with partial least-squares regression modeling. The ternary extrudates exhibited a dissolution profile similar to that of the 1:2 prepared eutectic, suggesting a physical distribution (or suspension) of the in situ synthesized eutectic contents within the polymeric matrix. |
| فهرسة مساهمة: | Keywords: albendazole; eutectic; mechanochemistry; multivariate analysis; partial least-squares regression; reactive extrusion |
| المشرفين على المادة: | 0 (Polymers) 0 (Maleates) 91XW058U2C (maleic acid) |
| تواريخ الأحداث: | Date Created: 20240813 Date Completed: 20240902 Latest Revision: 20240902 |
| رمز التحديث: | 20240902 |
| DOI: | 10.1021/acs.molpharmaceut.4c00152 |
| PMID: | 39135353 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1543-8392 |
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| DOI: | 10.1021/acs.molpharmaceut.4c00152 |