Masum Zia Uddin, Spoors P Grant, Burke Matt D, Gupta Vivek
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Stemline Therapeutics, Inc., A Menarini Group Company, 750 Lexington Avenue, 4th Floor, New York, NY 10022, USA.
Pharmaceutics. 2025 Jun 5;17(6):745. doi: 10.3390/pharmaceutics17060745.
This study expands on the polymorphic characterization of elacestrant dihydrochloride, developed by Stemline Therapeutics and approved by the FDA in 2023. The article focuses on more extensive polymorphism screening using various methods and solvents to discover the new polymorphism forms of this molecule, besides identifying three polymorphic forms in the previously published studies. The crystalline and amorphous elacestrant hydrochloride solubility was assessed, and crystals were formed, followed by polymorph screening using 40 non-conventional solvents via different techniques to obtain the new polymorphic forms. XRPD, NMR, DSC, TGA, IC, and HPLC were used for solid-state characterization. Patterns A, B, C, D, E, F, and G, and previously published forms 1,3, were identified in multiple studies during the extensive polymorphism screening using various methods and numerous solvent systems. Solid state characterization and purity analysis were completed using different relevant instruments. After the characterization, it was found that Pattern A was the most stable, like the desired/most stable Form 1, but it had fewer crystals; Pattern B is like Form 3 but a unique XRPD pattern; Pattern D is degradant; Pattern C, E, F, and G are considered as the new pattern of elacestrant along with patterns A and B. With XRPD, six new patterns (A, B, C, E, F, G) were identified. Patterns A, C, and E are promising crystalline candidates for further analysis and scale-up.
本研究扩展了由Stemline Therapeutics研发并于2023年获美国食品药品监督管理局（FDA）批准的盐酸艾拉司群的多晶型表征。除了在先前发表的研究中鉴定出三种多晶型形式外，本文重点使用各种方法和溶剂进行更广泛的多晶型筛选，以发现该分子的新多晶型形式。评估了结晶态和非晶态盐酸艾拉司群的溶解度，并形成晶体，随后通过不同技术使用40种非常规溶剂进行多晶型筛选以获得新的多晶型形式。使用X射线粉末衍射（XRPD）、核磁共振（NMR）、差示扫描量热法（DSC）、热重分析法（TGA）、离子色谱法（IC）和高效液相色谱法（HPLC）进行固态表征。在使用各种方法和众多溶剂系统进行的广泛多晶型筛选过程中的多项研究中，鉴定出了模式A、B、C、D、E、F和G以及先前发表的1、3型。使用不同的相关仪器完成了固态表征和纯度分析。表征后发现，模式A与所需的/最稳定的1型一样最稳定，但晶体较少；模式B与3型相似，但具有独特的XRPD图谱；模式D是降解产物；模式C、E、F和G与模式A和B一起被视为艾拉司群的新模式。通过XRPD，鉴定出六种新模式（A、B、C、E、F、G）。模式A、C和E是有前景的晶体候选物，可用于进一步分析和放大生产。
