کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484877 | 1114339 | 2012 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Rational Coformer or Solvent Selection for Pharmaceutical Cocrystallization or Desolvation
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
It is demonstrated that the fluid-phase thermodynamics theory conductor-like screening model for real solvents (COSMO-RS) as implemented in the COSMOtherm software can be used for accurate and efficient screening of coformers for active pharmaceutical ingredient (API) cocrystallization. The excess enthalpy, Hex, between an API-coformer mixture relative to the pure components reflects the tendency of those two compounds to cocrystallize. Thus, predictive calculations may be performed with decent effort on a large set of molecular data in order to identify potentially new cocrystal systems. In addition, it is demonstrated that COSMO-RS theory allows reasonable ranking of coformers for API solubility improvement. As a result, experiments may be focused on those coformers, which have an increased probability of cocrystallization, leading to the largest improvement of the API solubility. In a similar way as potential coformers are identified for cocrystallization, solvents that do not tend to form solvates may be determined based on the highest Hexs with the API. The approach was successfully tested on tyrosine kinase inhibitor axitinib, which has a propensity to form relatively stable solvated structures with the majority of common solvents, as well as on thiophanate-methyl and thiophanate-ethyl benzimidazole fungicides, which form channel solvates.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 10, October 2012, Pages 3687-3697
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 10, October 2012, Pages 3687-3697
نویسندگان
Yuriy A. Abramov, Christoph Loschen, Andreas Klamt,