de Boer A H, Le Brun P P H, van der Woude H G, Hagedoorn P, Heijerman H G M, Frijlink H W
Department of Pharmaceutical Technology and Biopharmacy, GUIDE: Groningen University Institute for Drug Exploration, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Eur J Pharm Biopharm. 2002 Jul;54(1):17-24. doi: 10.1016/s0939-6411(02)00043-7.
The aim of this study was to investigate the pulmonary administration of antibiotics as dry powder to patients with cystic fibrosis (CF), as an alternative for nebulization. This part of the study describes the development of a powder formulation with colistin sulfate as model substance. The aim of the new dosage form was to increase pulmonary deposition, therapeutic efficiency and, by that, compliance by the CF patients. A physical powder mixture of colistin and a size fraction of lactose (106-150 microm) was prepared and the mixture was optimized with respect to colistin content (83.3%) for use in a special test inhaler. A laser diffraction apparatus with special inhaler adapter was applied for analysis of the size distribution of the aerosol cloud from the inhaler. The size distributions of the aerosol clouds from the test inhaler at flow rates between 30 and 60 l/min for the optimized formulation showed nearly the same median diameter as that for the primary drug particles. But the X(100)-value was much lower, because of an effective large particle separation from the inspiratory air by an air classifier in the test inhaler. The results suggest that dry powder inhalation might be a suitable and highly efficient alternative for nebulization of antibiotic drugs in CF therapy.
本研究的目的是探讨将抗生素作为干粉剂经肺部给药用于囊性纤维化（CF）患者，作为雾化吸入的替代方法。本研究的这一部分描述了以硫酸黏菌素为模型物质的粉末制剂的研发过程。新剂型的目的是增加肺部沉积、提高治疗效果，从而提高CF患者的依从性。制备了黏菌素与乳糖特定粒度级分（106 - 150微米）的物理粉末混合物，并针对黏菌素含量（83.3%）对混合物进行了优化，以用于一种特殊的测试吸入器。使用配备特殊吸入器适配器的激光衍射仪分析来自吸入器的气溶胶云的粒度分布。对于优化后的制剂，在30至60升/分钟的流速下，测试吸入器产生的气溶胶云的粒度分布显示其平均直径与原药颗粒的平均直径几乎相同。但由于测试吸入器中的空气分级器能有效分离吸入空气中的大颗粒，其X(100)值要低得多。结果表明，干粉吸入可能是CF治疗中抗生素药物雾化吸入的一种合适且高效的替代方法。
