Nakano T, Yuasa H
Laboratory of Medical and Pharmaceutical Technology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, 192-0392, Tokyo, Japan.
Int J Pharm. 2001 Mar 14;215(1-2):3-12. doi: 10.1016/s0378-5173(00)00620-7.
We previously reported that sodium citrate (Na citrate), which is a high order salt in the Hofmeister's series, greatly suppressed particle agglomeration in fluidized bed coating (Pharm. Res., 16 (1999), 1616-1620). In this paper, we studied the effects of Na citrate concentration on the particle agglomeration in fluidized bed coating and on the structure of coated film on the particles. Spherical granules made of crystalline cellulose (Celphere) containing phenacetin were coated in a fluidized bed with the aqueous coating solution of hydroxypropylmethyl cellulose (HPMC) containing Na citrate at various concentrations. The particle diameter and drug release profile of coated particles, and the physical properties, i.e. tensile strength, elongation percentage at break, porosity and pore size distribution, of the HPMC cast film were investigated. The particle agglomeration was suppressed with the increasing Na citrate concentration. It is considered that the increase in the suppression effect was caused by the salting-out effect of the increased Na citrate. In the HPMC cast film system, the tensile strength and elongation percentage decreased and the porosity and cumulative pore volume increased with an increase in Na citrate concentration. It is considered that the increase in the porosity by adding Na citrate resulted from a phase separation due to the salting-out during the film forming process. The drug release rate from coated particles also increased with the increasing Na citrate concentration. It can be concluded that the increase in the release rate was due to the increase in porosity of the HPMC coated film caused by the increased Na citrate concentration.
我们之前报道过，柠檬酸钠（Na柠檬酸盐）作为霍夫迈斯特序列中的高阶盐，在流化床包衣中能极大地抑制颗粒团聚（《药物研究》，16 (1999)，1616 - 1620）。在本文中，我们研究了柠檬酸钠浓度对流化床包衣中颗粒团聚以及颗粒表面包衣膜结构的影响。由含有非那西丁的结晶纤维素（Celphere）制成的球形颗粒，在流化床中用含有不同浓度柠檬酸钠的羟丙基甲基纤维素（HPMC）水性包衣溶液进行包衣。研究了包衣颗粒的粒径和药物释放曲线，以及HPMC流延膜的物理性能，即拉伸强度、断裂伸长率、孔隙率和孔径分布。随着柠檬酸钠浓度的增加，颗粒团聚受到抑制。据认为，抑制效果的增强是由柠檬酸钠增加所产生的盐析效应导致的。在HPMC流延膜体系中，随着柠檬酸钠浓度的增加，拉伸强度和断裂伸长率降低，孔隙率和累积孔体积增加。据认为，添加柠檬酸钠导致孔隙率增加是由于成膜过程中盐析引起的相分离。包衣颗粒的药物释放速率也随着柠檬酸钠浓度的增加而增加。可以得出结论，释放速率的增加是由于柠檬酸钠浓度增加导致HPMC包衣膜孔隙率增加所致。
