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载有硫酸沙丁胺醇的卡波姆改性喷雾干燥吸入粉末。

Carbomer-modified spray-dried respirable powders for pulmonary delivery of salbutamol sulphate.

机构信息

Aston Pharmacy School, Aston University, Birmingham, UK.

出版信息

J Microencapsul. 2009 Aug;26(5):444-55. doi: 10.1080/02652040802456924.

Abstract

The present study investigates the feasibility of using two types of carbomer (971 and 974) to prepare inhalable dry powders that exhibit modified drug release properties. Powders were prepared by spray-drying formulations containing salbutamol sulphate, 20-50% w/w carbomer as a drug release modifier and leucine as an aerosolization enhancer. Following physical characterization of the powders, the aerosolization and dissolution properties of the powders were investigated using a Multi-Stage Liquid Impinger and a modified USP II dissolution apparatus, respectively. All carbomer 974-modified powders and the 20% carbomer 971 powder demonstrated high dispersibility, with emitted doses of at least 80% and fine particle fractions of approximately 40%. The release data indicated that all carbomer-modified powders displayed a sustained release profile, with carbomer 971-modified powders obeying first order kinetics, whereas carbomer 974-modified powders obeyed the Higuchi root time kinetic model; increasing the amount of carbomer 971 in the formulation did not extend the duration of drug release, whereas this was observed for the carbomer 974-modified powders. These powders would be anticipated to deposit predominately in the lower regions of the lung following inhalation and then undergo delayed rather than instantaneous drug release, offering the potential to reduce dosing frequency and improve patient compliance.

摘要

本研究旨在探讨使用两种类型的卡波姆(971 和 974)来制备具有改良药物释放特性的可吸入干粉的可行性。通过喷雾干燥法制备含有硫酸沙丁胺醇、20-50%w/w 卡波姆作为药物释放调节剂和亮氨酸作为气溶胶增强剂的配方粉末。对粉末进行物理特性表征后,分别使用多阶段液体撞击器和改良的 USP II 溶解装置研究粉末的气溶胶化和溶解特性。所有的卡波姆 974 改性粉末和 20%卡波姆 971 粉末都表现出高分散性,发射剂量至少为 80%,细颗粒分数约为 40%。释放数据表明,所有卡波姆改性粉末都表现出持续释放的特征,其中卡波姆 971 改性粉末遵循一级动力学,而卡波姆 974 改性粉末则遵循 Higuchi 根时间动力学模型;在制剂中增加卡波姆 971 的量并不能延长药物释放的持续时间,但在卡波姆 974 改性粉末中观察到了这种情况。这些粉末在吸入后预计会主要沉积在肺部的下部区域,然后经历延迟而不是即时的药物释放,从而有可能减少给药频率并提高患者的依从性。

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