Younis Islam R, Stamatakis Mary K, Callery Patrick S, Meyer-Stout Paula Jo
Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, Morgantown, WV 26506, United States.
Int J Pharm. 2009 Feb 9;367(1-2):97-102. doi: 10.1016/j.ijpharm.2008.09.028. Epub 2008 Sep 25.
The vitamin folic acid has received considerable attention because of its role in decreasing the risk of neural tube birth defects, and its potential role in reducing the risks of cardiovascular and psychiatric diseases. A significant concern is the quality of commercially available folic acid products. We evaluated the pharmaceutical performance of 15 currently available folic acid products in terms of meeting the USP standards for disintegration and dissolution, and showed that there has been significant improvement in the past decade in the quality of these products. However, at least one product failed to meet the requirement of each test performed. Since folic acid absorption is maximal at the proximal jejunum, dissolution was further evaluated in simulated gastric fluid. All the products failed to release more than 75% of the active ingredient in 60min. While some excipient-related factors were preliminarily considered, it was ultimately proposed that the failure may be related to the pH-dependency of the solubility of folic acid, a premise supported by faster dissolution of laboratory prepared buffered folic acid tablets. The more limited solubility of folic acid in acidic medium should be taken into consideration in the required dissolution testing methods, as well as in product formulation to optimize release.
维生素叶酸因其在降低神经管出生缺陷风险方面的作用以及在降低心血管疾病和精神疾病风险方面的潜在作用而受到广泛关注。一个重大问题是市售叶酸产品的质量。我们根据符合美国药典（USP）崩解和溶出标准对15种市售叶酸产品的药学性能进行了评估，结果表明这些产品的质量在过去十年中有了显著提高。然而，至少有一种产品未能满足所进行的每项测试的要求。由于叶酸在空肠近端的吸收最大，因此在模拟胃液中进一步评估了溶出情况。所有产品在60分钟内释放的活性成分均未超过75%。虽然初步考虑了一些与辅料相关的因素，但最终认为失败可能与叶酸溶解度的pH依赖性有关，实验室制备的缓冲叶酸片更快的溶出情况支持了这一前提。在所需的溶出度测试方法以及产品配方中，应考虑叶酸在酸性介质中溶解度更有限的情况，以优化释放。
