Computational polymorph screening reveals late-appearing and poorly-soluble form of rotigotine
| Autor: | Johannes Hoja, Luc Quere, Marcus A. Neumann, Majid Mortazavi, Luc Aerts, Alexandre Tkatchenko, Jacco van de Streek |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Active ingredient
Chemistry Rotigotine General Chemistry Biochemistry Combinatorial chemistry Relative stability Crystal structure prediction lcsh:Chemistry Chemistry [G01] [Physical chemical mathematical & earth Sciences] lcsh:QD1-999 Chimie [G01] [Physique chimie mathématiques & sciences de la terre] Materials Chemistry medicine Environmental Chemistry Prior information medicine.drug |
| Zdroj: | Communications Chemistry, 2, 70. London, United Kingdom: Springer Nature (2019). Communications Chemistry Communications Chemistry, Vol 2, Iss 1, Pp 1-7 (2019) |
| ISSN: | 2399-3669 |
| DOI: | 10.1038/s42004-019-0171-y |
| Popis: | The active pharmaceutical ingredient rotigotine—a dopamine agonist for the treatment of Parkinson’s and restless leg diseases—was known to exist in only one polymorphic form since 1985. In 2008, the appearance of a thermodynamically more stable and significantly less soluble polymorph led to a massive batch recall followed by economic and public health implications. Here, we carry out state-of-the-art computational crystal structure prediction, revealing the late-appearing polymorph without using any prior information. In addition, we predict a third crystalline form of rotigotine having thermodynamic stability between forms I and II. We provide quantitative description of the relative stability and solubility of the rotigotine polymorphs. Our study offers new insights into a challenging polymorphic system and highlights the robustness of contemporary computational crystal structure prediction during pharmaceutical development. It is important to screen potentially polymorphic systems during pharmaceutical development. Here, the authors demonstrate computational crystal structure prediction analysis which is capable of identifying the late appearing low-solubility polymorph of rotigotine without prior information. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|