Islam Nazrul, Stewart Peter, Larson Ian, Hartley Patrick
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville Vic 3052, Australia.
J Pharm Sci. 2004 Apr;93(4):1030-8. doi: 10.1002/jps.10583.
The objective of this study was to determine the influence of lactose carrier size on drug dispersion of salmeterol xinafoate (SX) from interactive mixtures. SX dispersion was measured by using the fine particle fractions determined by a twin stage impinger attached to a Rotahaler. The particle size of the lactose carrier in the SX interactive mixtures was varied using a range of commercial inhalation-grade lactoses. In addition, differing size fractions of individual lactose samples were achieved by dry sieving. The dispersion of SX appeared to increase as the particle size of the lactose carrier decreased for the mixtures prepared from different particle size commercial samples of lactose and from different sieve fractions of the same lactose. Fine particles of lactose (<5 microm) associated with the lactose carrier were removed from the carrier surface by a wet decantation process to produce lactose samples with low but similar concentrations of fine lactose particles. The fine particle fractions of SX in mixtures prepared with the decanted lactose decreased significantly (analysis of variance, p < 0.001) and the degree of dispersion became independent of the volume mean diameter of the carriers (analysis of variance, p < 0.05). The dispersion behavior is therefore associated with the presence of fine adhered particles associated with the carriers and the inherent size of the carrier itself has little influence on dispersion.
本研究的目的是确定乳糖载体大小对昔萘酸沙美特罗（SX）从交互式混合物中药物分散的影响。通过使用连接到旋转吸入器的双级撞击器测定的细颗粒部分来测量SX的分散度。使用一系列商业吸入级乳糖改变SX交互式混合物中乳糖载体的粒径。此外，通过干筛获得各个乳糖样品的不同粒度部分。对于由不同粒度的商业乳糖样品和同一乳糖的不同筛分级分制备的混合物，随着乳糖载体粒径的减小，SX的分散度似乎增加。通过湿倾析法从载体表面除去与乳糖载体相关的乳糖细颗粒（<5微米），以制备具有低但相似浓度的乳糖细颗粒的乳糖样品。用倾析乳糖制备的混合物中SX的细颗粒部分显著降低（方差分析，p <0.001），并且分散度变得与载体的体积平均直径无关（方差分析，p <0.05）。因此，分散行为与载体上附着的细颗粒的存在有关，而载体本身的固有尺寸对分散影响很小。
