Pharmaceutical Technology Laboratory, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Int J Pharm. 2010 Apr 15;389(1-2):74-85. doi: 10.1016/j.ijpharm.2010.01.021. Epub 2010 Jan 18.
The effect of morphology and surface characteristics of carriers were investigated for development of dry powder inhaler (DPI) formulation of insulin-loaded poly (D,L-lactic-co-glycolic acid) microcapsules for sustained-release pulmonary delivery of insulin. Microcapsule/carrier powder mixtures were prepared consisting of insulin-loaded PLGA microcapsules and sorbitol or mannitol as the carriers with various particle surface morphologies prepared by spray-drying and freeze-drying techniques. Powders were assessed by particle size analyzer, scanning electron microscopy, surface area analyzer, atomic force microscopy, helium pycnometer, X-ray diffraction, differential scanning calorimetery, bulk and tapped densitometers. Aerosol dispersion of microcapsules was examined by a twin impinger using Spinhaler device. The flowability results showed that the lowest (27.51+/-2.24%) and the highest (48.53+/-3.36%) Carr's indices were obtained for the samples containing sieved mannitol and spray-dried mannitol, respectively. The in vitro inhalation properties of the powder mixture prepared using various carrier shape and surface morphology were different, suggesting that the separation of microcapsules from carrier was a determining step to improve inhalation properties of DPIs. The results showed that the highest fine particle fraction (18.3+/-1.65%) and fine particle dose (62.22+/-3.74 microg) were obtained for the microcapsules formulated with sieved mannitol and these values were the lowest when the sieved mannitol was replaced by sieved sorbitol (10.5+/-0.86% and 35.70+/-2.51 microg). It was concluded that optimization of surface roughness is a critical parameter in development of DPIs. It also suggested that the elongation of carrier particles may play an important role in determining the aerosolization properties of the microcapsules. It seems that decrease in crystalline content of carriers may contribute to a decreased in fine particle fraction delivered.
研究了载体的形态和表面特性对载胰岛素聚（D，L-丙交酯-共-乙交酯）微囊干粉吸入剂（DPI）制剂的开发的影响，该微囊用于胰岛素的持续释放肺部递药。用喷雾干燥和冷冻干燥技术制备了由胰岛素负载的 PLGA 微囊和山梨醇或甘露醇作为载体的微囊/载体粉末混合物，其中包含具有各种颗粒表面形态的微囊/载体粉末混合物。通过粒度分析仪、扫描电子显微镜、比表面积分析仪、原子力显微镜、氦比重瓶、X 射线衍射仪、差示扫描量热仪、散装和振实密度计评估粉末。使用 Spinhaler 装置的双冲击器检查微囊的空气分散体。结果表明，含有过筛甘露醇和喷雾干燥甘露醇的样品的最低（27.51+/-2.24%）和最高（48.53+/-3.36%）Carr 指数。使用各种载体形状和表面形态制备的粉末混合物的体外吸入性质不同，表明从载体中分离微囊是改善 DPI 吸入性质的决定性步骤。结果表明，用过筛甘露醇配制的微囊的微细粒子分数（18.3+/-1.65%）和微细粒子剂量（62.22+/-3.74μg）最高，而用过筛甘露醇代替过筛甘露醇时，微细粒子分数（10.5+/-0.86%）和微细粒子剂量（35.70+/-2.51μg）最低。研究表明，优化表面粗糙度是开发 DPI 的关键参数。这也表明载体颗粒的伸长可能在确定微囊的空气动力学性质方面发挥重要作用。似乎载体结晶度的降低可能导致递送的微细粒子分数降低。
