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Solvent Vapor Annealing of Amorphous Carbamazepine Films for Fast Polymorph Screening and Dissolution Alteration
ACS Omega ( IF 4.1 ) Pub Date : 2017-09-07 00:00:00 , DOI: 10.1021/acsomega.7b00783
Benedikt Schrode 1, 2 , Brigitta Bodak 1 , Hans Riegler 1 , Andreas Zimmer 1 , Paul Christian 2 , Oliver Werzer 1
Affiliation  

Solubility enhancement and thus higher bioavailability are of great importance and a constant challenge in pharmaceutical research whereby polymorph screening and selection is one of the most important tasks. A very promising approach for polymorph screening is solvent vapor annealing where a sample is exposed to an atmosphere saturated with molecules of a specific chemical/solvent. In this work, amorphous carbamazepine thin films were prepared by spin coating, and the transformation into crystalline forms under exposure to solvent vapors was investigated. Employing grazing incidence X-ray diffraction, four distinct carbamazepine polymorphs, a solvate, and hydrates could be identified, while optical microscopy showed mainly spherulitic morphologies. In vitro dissolution experiments revealed different carbamazepine release from the various thin-film samples containing distinct polymorphic compositions: heat treatment of amorphous samples at 80 °C results in an immediate release; samples exposed to EtOH vapors show a drug release about 5 times slower than this immediate one; and all the others had intermediate release profiles. Noteworthy, even the sample of slowest release has a manifold faster release compared to a standard powder sample demonstrating the capabilities of thin-film preparation for faster drug release in general. Despite the small number of samples in this screening experiment, the results clearly show how solvent vapor annealing can assist in identifying potential polymorphs and allows for estimating their impact on properties like bioavailability.

中文翻译:

非晶态卡马西平薄膜的溶剂蒸气退火,用于快速多晶型物筛选和溶解度改变

在药物研究中,提高溶解度并因此提高生物利用度非常重要,这也是一个持续的挑战,而多晶型物的筛选和选择是最重要的任务之一。用于多晶型物筛选的一种非常有前途的方法是溶剂蒸汽退火,其中将样品暴露于特定化学/溶剂分子饱和的气氛中。在这项工作中,通过旋涂制备非晶态卡马西平薄膜,并研究了在暴露于溶剂蒸气下的转变为结晶形式。利用掠入射X射线衍射,可以鉴定出四种不同的卡马西平多晶型物,溶剂化物和水合物,而光学显微镜显示的主要是球状形态。体外溶出实验表明,不同的卡马西平从不同的薄膜样品中释放出不同的含量,这些薄膜样品中包含不同的多晶型物:80°C时对无定形样品进行热处理可立即释放;暴露于EtOH蒸气的样品显示,药物释放的速度比立即释放的药物慢约5倍;其他所有版本都有中间版本配置文件。值得注意的是,与标准粉末样品相比,即使是释放速度最慢的样品也具有较快的释放速度,这证明了薄膜制备通常具有更快的药物释放能力。尽管此筛选实验中的样品数量很少,但结果清楚地表明了溶剂蒸气退火如何有助于识别潜在的多晶型物,并允许估算其对诸如生物利用度之类的特性的影响。
更新日期:2017-09-07
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