Nocent M, Bertocchi L, Espitalier F, Baron M, Couarraze G
GlaxoSmithkline Laboratories, Pharmaceutical Development Department, Zone Industrielle n degrees 2, 23 Rue Lavoisier, 27000 EVREUX, France.
J Pharm Sci. 2001 Oct;90(10):1620-7. doi: 10.1002/jps.1112.
In this paper we describe how the spherical crystallization process by QESD method can be applied to a water-soluble drug, salbutamol sulfate. The type of solvent, antisolvent, and emulsifier and the concentration of emulsifier to be used for the production of spherical particles with a size range 80-500 microm are determined. Furthermore, the solvent/antisolvent ratio and the temperature difference between them (Delta T) are studied. It was observed that, in the case of salbutamol sulfate, the Delta T value has no influence on the formation of spherical particles. A very large metastable zone of salbutamol sulfate in water could explain this phenomenon. Finally, the influence of emulsifier concentration and of maturation time on the size of spherical particles is studied. The results show that these two parameters must be fixed to control the size of the recovered particles.
在本文中，我们描述了如何通过QESD方法将球形结晶过程应用于水溶性药物硫酸沙丁胺醇。确定了用于生产尺寸范围为80 - 500微米球形颗粒的溶剂、反溶剂、乳化剂类型以及乳化剂浓度。此外，还研究了溶剂/反溶剂比例及其之间的温差（ΔT）。观察到，对于硫酸沙丁胺醇而言，ΔT值对球形颗粒的形成没有影响。硫酸沙丁胺醇在水中存在非常大的亚稳区可以解释这一现象。最后，研究了乳化剂浓度和熟化时间对球形颗粒尺寸的影响。结果表明，必须固定这两个参数以控制回收颗粒的尺寸。
