Bai Ge, Armenante Piero M, Plank Russell V
New Jersey Institute of Technology, Otto H. York Department of Chemical Engineering, 323 M. L. King Boulevard, Newark, New Jersey 07102-1982, USA.
J Pharm Sci. 2007 Nov;96(11):3072-86. doi: 10.1002/jps.20994.
Blend time, the time to achieve a predefined level of homogeneity of a tracer in a mixing vessel, is an important parameter to evaluate the mixing efficiency of mixing devices. In this work, the blend time required to homogenize the liquid content of a USP Dissolution Testing Apparatus II under a number of operating conditions was obtained using two different experimental methods (tracer detection via colorimetric and conductivity measurements), a computational approach (computational fluid dynamics (CFD)), and a semi-theoretical analysis of the phenomenon. Under the standard geometric and operating conditions in which the USP Apparatus II is typically used (N = 50 rpm) the experimental blend time to achieve a 92.74% uniformity level was found to be between 27.5 and 33.3 s, depending on the location of the injection point and monitoring point for the tracer. These values were in close agreement with those obtained from CFD simulations. Changing the impeller vertical position (+/-2 mm) had only a limited effect. The CFD predictions also indicated that blend time is inversely proportional to the agitation speed. This conclusion is in agreement with previous reports and equations for blend time in mixing vessels. The blend times obtained in this work appear to be some two orders of magnitude smaller than the time usually required for appreciable tablet dissolution during the typical dissolution test, implying that the liquid contents of the USP Apparatus II can be considered to be relatively well mixed during the typical dissolution test.
混合时间是指在混合容器中使示踪剂达到预定均匀度水平所需的时间，是评估混合设备混合效率的一个重要参数。在本研究中，采用两种不同的实验方法（通过比色法和电导率测量检测示踪剂）、一种计算方法（计算流体动力学（CFD））以及对该现象的半理论分析，得出了在多种操作条件下使美国药典溶出度测试装置II中的液体内容物均匀化所需的混合时间。在通常使用美国药典装置II的标准几何和操作条件下（转速N = 50 rpm），根据示踪剂注入点和监测点的位置，达到92.74%均匀度水平的实验混合时间在27.5至33.3秒之间。这些值与CFD模拟得到的值非常吻合。改变叶轮垂直位置（±2毫米）的影响有限。CFD预测还表明，混合时间与搅拌速度成反比。这一结论与之前关于混合容器中混合时间的报告和公式一致。本研究中获得的混合时间似乎比典型溶出度测试中片剂明显溶解通常所需的时间小约两个数量级，这意味着在典型溶出度测试期间，美国药典装置II中的液体内容物可被认为混合得相对良好。
