Simon Alice, Amaro Maria Inês, Cabral Lucio Mendes, Healy Anne Marie, de Sousa Valeria Pereira
Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Bss, sl15, Rio de Janeiro, RJ 21941-902, Brazil; School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
Int J Pharm. 2016 Mar 30;501(1-2):124-38. doi: 10.1016/j.ijpharm.2016.01.066. Epub 2016 Feb 1.
The purpose of this study was to prepare engineered particles of rivastigmine hydrogen tartrate (RHT) and to characterize the physicochemical and aerodynamic properties, in comparison to a lactose carrier formulation (LCF). Microparticles were prepared from ethanol/water solutions containing RHT with and without the incorporation of L-leucine (Leu), using a spray dryer. Dry powder inhaler formulations prepared were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, ATR-FTIR, differential scanning calorimetry, bulk and tapped density, dynamic vapour sorption and in vitro aerosol deposition behaviour using a next generation impactor. The smooth-surfaced spherical morphology of the spray dried microparticles was altered by adding Leu, resulting in particles becoming increasingly wrinkled with increasing Leu. Powders presented low densities. The glass transition temperature was sufficiently high (>90 °C) to suggest good stability at room temperature. As Leu content increased, spray dried powders presented lower residual solvent content, lower particle size, higher fine particle fraction (FPF<5 μm), and lower mass median aerodynamic diameter (MMAD). The LCF showed a lower FPF and higher MMAD, relative to the spray dried formulations containing more than 10% Leu. Spray dried RHT powders presented better aerodynamic properties, constituting a potential drug delivery system for oral inhalation.
本研究的目的是制备酒石酸氢卡巴拉汀（RHT）工程颗粒，并与乳糖载体制剂（LCF）相比，对其物理化学和空气动力学性质进行表征。使用喷雾干燥器，从含有RHT且添加或不添加L-亮氨酸（Leu）的乙醇/水溶液中制备微粒。通过扫描电子显微镜、粉末X射线衍射、激光衍射粒度分析、衰减全反射傅里叶变换红外光谱、差示扫描量热法、松装密度和振实密度、动态蒸汽吸附以及使用下一代撞击器的体外气溶胶沉积行为，对所制备的干粉吸入剂制剂进行表征。添加Leu会改变喷雾干燥微粒的光滑表面球形形态，导致颗粒随着Leu含量增加而变得越来越皱。粉末呈现低密度。玻璃化转变温度足够高（>90°C），表明在室温下具有良好的稳定性。随着Leu含量增加，喷雾干燥粉末的残留溶剂含量降低、粒径减小、细颗粒分数（FPF<5μm）增加，质量中值空气动力学直径（MMAD）降低。相对于含有超过10%Leu的喷雾干燥制剂，LCF显示出较低的FPF和较高的MMAD。喷雾干燥的RHT粉末具有更好的空气动力学性质，构成了一种潜在的口服吸入药物递送系统。
