Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, New Jersey, USA.
Drug Dev Ind Pharm. 2011 Aug;37(8):963-76. doi: 10.3109/03639045.2010.551775. Epub 2011 Feb 16.
Micronization and nanoparticle production of poorly water-soluble drugs was investigated using single wet milling equipment operating in the attritor and stirred media modes. The drug particles in the median size range of 0.2?2??m were prepared by changing the milling mode and operating conditions of a Micros mill with a purpose of elucidating the dynamics of the wet milling process. It was determined that particle breakage due to mechanical stresses and aggregation due to insufficient stabilization are two competing mechanisms which together control the wet milling dynamics of the poorly water-soluble drugs. The study in the attritor mode using four different classes of stabilizers with six drugs indicated that steric stabilization worked better than electrostatic stabilization for the drugs studied. In addition, the existence of different minimum polymer concentrations for the stabilization of microsuspensions and nanosuspensions was indicated. The major role of a non-ionic polymer during the production of fine particles is its stabilization action through steric effects, and no experimental evidence was found to support the so-called Rehbinder effect. Periodic addition of the polymer as opposed to the addition of the polymer at the start of milling process was introduced as a novel processing method. This novel method of polymer addition provided effective stabilization and breakage of drug particles leading to a narrower and finer particle size distribution. Alternatively, it may allow shorter processing time and lower overall power consumption of the milling process for a desired particle size.
采用搅拌磨和搅拌球磨机两种湿法研磨设备，研究了难溶性药物的超微细化和纳米化。通过改变 Micros 磨的研磨方式和操作条件，制备了中值粒径范围在 0.2?2??m 的药物颗粒，以阐明湿法研磨过程的动力学。研究结果表明，药物颗粒的破碎是由机械应力引起的，而团聚则是由于稳定性不足引起的，这两个竞争机制共同控制着难溶性药物的湿法研磨动力学。在搅拌磨中使用四种不同类型的稳定剂对六种药物进行了研究，结果表明，对于所研究的药物，空间位阻稳定作用优于静电稳定作用。此外，还表明存在不同的最小聚合物浓度，用于稳定微悬浮液和纳米悬浮液。在制备细颗粒过程中，非离子聚合物的主要作用是通过空间位阻作用进行稳定，没有实验证据支持所谓的 Rehbinder 效应。与在研磨过程开始时添加聚合物相反，周期性添加聚合物被引入作为一种新的加工方法。这种添加聚合物的新方法可有效稳定和破碎药物颗粒，从而得到更窄和更细的粒径分布。或者，它可能允许在所需粒径下，缩短加工时间并降低研磨过程的总能耗。
