Mantas Athanasios, Mihranyan Albert
Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, 75121 Uppsala, Sweden.
Pharmaceutics. 2019 Jan 18;11(1):37. doi: 10.3390/pharmaceutics11010037.
Nifedipine (NIF) is a 1,4-dihydropyridine-based calcium channel blocker with poor solubility, whose bioavailability is highly dependent on the type of formulation. Dry powder mixtures of 20% / NIF with microcrystalline cellulose (MCC) and its high surface area nanocellulose analogue, which is namely Cladophora (CLAD) cellulose, were produced by heating at the melting temperature of the drug for 1 h. Non-heated samples were used as a reference. The solid-state properties of the mixtures were characterized by scanning electron microscopy, differential scanning calorimetry and X-ray diffraction. The drug release was studied in biorelevant media, including simulated gastric fluid (SGF), fasted-state simulated intestinal fluid (FaSIF) and fed-state simulated intestinal fluid (FeSIF). An enhanced apparent solubility and faster dissolution rate of NIF were observed in the heated mixture of NIF with CLAD-H in all tested biorelevant media (i.e., SGF, FaSIF and FeSIF), which was due to NIF amorphization in the high surface area nanocellulose powder. Ordinary MCC, which is essentially non-porous, did not produce an enhancement of a similar magnitude. The results of the study suggest that dry powder formulation using high surface area nanocellulose is a facile new strategy for formulating calcium channel blocker drugs, which could potentially be a viable alternative to currently used soft gel liquid capsules.
硝苯地平（NIF）是一种基于1,4 - 二氢吡啶的钙通道阻滞剂，溶解度较差，其生物利用度高度依赖于制剂类型。通过在药物熔点加热1小时，制备了含20% NIF与微晶纤维素（MCC）及其高比表面积纳米纤维素类似物（即枝管藻（CLAD）纤维素）的干粉混合物。未加热的样品用作对照。通过扫描电子显微镜、差示扫描量热法和X射线衍射对混合物的固态性质进行了表征。在生物相关介质中研究了药物释放情况，这些介质包括模拟胃液（SGF）、禁食状态模拟肠液（FaSIF）和进食状态模拟肠液（FeSIF）。在所有测试的生物相关介质（即SGF、FaSIF和FeSIF）中，在NIF与CLAD - H的加热混合物中观察到NIF的表观溶解度增强和溶解速率加快，这是由于NIF在高比表面积纳米纤维素粉末中形成了无定形状态。普通的基本上无孔的MCC并未产生类似程度的增强效果。研究结果表明，使用高比表面积纳米纤维素的干粉制剂是一种简便的新策略，可用于配制钙通道阻滞剂药物，这可能是目前使用的软胶囊液体胶囊的一种可行替代方案。
