Schrode Benedikt, Bodak Brigitta, Riegler Hans, Zimmer Andreas, Christian Paul, Werzer Oliver
Institute of Pharmaceutical Sciences, NAWI Graz, Department of Pharmaceutical Technology, University Graz, Universtitätsplatz 1, 8010 Graz, Austria.
Institute for Solid State Physics, NAWI Graz, Graz University of Technology, Petersgasse 16, 8010 Graz, Austria.
ACS Omega. 2017 Sep 30;2(9):5582-5590. doi: 10.1021/acsomega.7b00783. Epub 2017 Sep 7.
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. 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.
在药物研究中，提高溶解度进而提高生物利用度至关重要且一直是一项挑战，其中多晶型筛选和选择是最重要的任务之一。一种非常有前景的多晶型筛选方法是溶剂蒸汽退火，即将样品暴露于含有特定化学物质/溶剂分子的饱和气氛中。在这项工作中，通过旋涂制备了无定形卡马西平薄膜，并研究了在溶剂蒸汽作用下向结晶形式的转变。采用掠入射X射线衍射，可以识别出四种不同的卡马西平多晶型、一种溶剂化物和水合物，而光学显微镜主要显示出球晶形态。溶解实验揭示了不同的卡马西平从含有不同多晶型组成的各种薄膜样品中的释放情况：无定形样品在80°C下热处理会导致立即释放；暴露于乙醇蒸汽的样品显示药物释放速度比立即释放的情况慢约5倍；其他所有样品的释放曲线都处于中间状态。值得注意的是，即使是释放最慢的样品，与标准粉末样品相比，其释放速度也快得多，这总体上证明了薄膜制备在实现更快药物释放方面的能力。尽管在这个筛选实验中的样品数量较少，但结果清楚地表明溶剂蒸汽退火如何有助于识别潜在的多晶型，并能够评估它们对生物利用度等性质的影响。
