Department of Industrial Pharmacy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku, Nagoya 468-8503, Japan.
Int J Pharm. 2009 Dec 1;382(1-2):88-97. doi: 10.1016/j.ijpharm.2009.08.011. Epub 2009 Aug 15.
Spray freeze-drying (SFD) process, which is a novel particle design technique previously developed by authors, has been improved by using four-fluid nozzle (4N) instead of conventional two-fluid nozzle (2N) to expand its application in pharmaceutical industry. Aqueous spray solutions of the drug and the polymeric carrier were separately supplied into 4N, and atomized while colliding with each other at the tip of nozzle. The droplets of mixed solutions were directly immersed into liquid nitrogen and immediately frozen to form a suspension. Then, the iced droplets were lyophilized by freeze-dryer to prepare the composite particles of the drug and carrier. This process has been used in the present study to modify and enhance the dissolution profiles of poorly water-soluble drug, phenytoin. Water-soluble and enteric polymeric carriers in pharmaceutical use were used as a dissolution modifier. The SFD composite particles prepared by using 4N were fully characterized compared to those using 2N from morphological and physicochemical perspectives. It was found that the particles have fine porous structure producing vast specific surface area. Further, phenytoin was completely dispersed as amorphous state in the polymeric matrix with higher carrier ratio than phenytoin:carrier = 1:3. The dissolution of phenytoin from the water-soluble carrier-based particles was greatly enhanced because of large effective surface area and disappearance of crystalline. On the other hand, the release profiles from enteric carrier-based particles showed the typical enteric patterns, that is, delayed in acidic medium and accelerated in neutral pH. The results demonstrated that SFD technique using 4N has potential to develop the novel solubilized formulation for poorly water-soluble APIs.
喷雾冷冻干燥（SFD）工艺是一种新型的颗粒设计技术，由作者先前开发，通过使用四流体喷嘴（4N）代替传统的双流体喷嘴（2N）对其进行了改进，以扩大其在制药行业的应用。药物和聚合物载体的水性喷雾溶液分别供应到 4N，并在喷嘴尖端相互碰撞时雾化。混合溶液的液滴直接浸入液氮中并立即冻结以形成悬浮液。然后，通过冷冻干燥机对冰滴进行冷冻干燥以制备药物和载体的复合颗粒。本研究中使用该工艺来修饰和增强水溶性差的药物苯妥英的溶解曲线。使用了药用的水溶性和肠溶聚合物载体作为溶解改性剂。与使用 2N 相比，使用 4N 制备的 SFD 复合颗粒在形态和物理化学方面都得到了充分的表征。结果发现，颗粒具有精细的多孔结构，产生了巨大的比表面积。此外，由于较大的有效表面积和无定形状态的存在，苯妥英在聚合物基质中的分散度更高，载药比为 1:3。基于水溶性载体的颗粒中的苯妥英的溶解得到了极大的增强，因为其具有较大的有效表面积和消失的结晶性。另一方面，基于肠溶载体的颗粒的释放曲线表现出典型的肠溶模式，即在酸性介质中延迟，在中性 pH 中加速。结果表明，使用 4N 的 SFD 技术有潜力开发用于水溶性差的 API 的新型增溶配方。
