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通过精密包衣将细颗粒固定在乳糖载体上及其对干粉制剂性能的影响。

Immobilization of fine particles on lactose carrier by precision coating and its effect on the performance of dry powder formulations.

作者信息

Chan Lai Wah, Lim Liang Theng, Heng Paul W S

机构信息

Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Republic of Singapore.

出版信息

J Pharm Sci. 2003 May;92(5):975-84. doi: 10.1002/jps.10372.

Abstract

The feasibility of immobilization of fine particles on a lactose carrier by precision coating and producing carrier particles of different surface roughness from the same core was explored. A relationship between the resultant surface roughness of the carrier and the in vitro deposition pattern of salbutamol sulfate was established. Lactose carrier particles in the precision coating chamber were spray coated with liquid suspensions consisting of micronized lactose dispersed in isopropyl alcohol (IPA) and/or water mixtures. The surface-modified lactose particles were fractionated and then characterized by laser diffraction for size, image analysis for shape, and scanning probe microscopy for surface roughness. The in vitro deposition pattern of salbutamol sulfate from the drug-lactose mixtures was determined with the twin-stage glass impinger and expressed as the fine particle fraction and dispersibility of the drug. Immobilization of fine particles on carrier particles was feasible by the precision coating process as shown by the scanning probe topographs and the roughness values of the carrier particles. Generally, more discrete fine particles were deposited on the carrier surface and a higher surface roughness was seen when the spray suspension consisting of a higher proportion of IPA was used. A significant correlation was found between the fine particle fraction of salbutamol sulfate with the roughness of lactose. This relationship established between the in vitro drug deposition pattern and the microscopic surface roughness of the carrier would be helpful in the optimization of drug delivery to targeted areas in the lungs.

摘要

探讨了通过精密包衣将细颗粒固定在乳糖载体上并从同一核心制备具有不同表面粗糙度的载体颗粒的可行性。建立了载体最终表面粗糙度与硫酸沙丁胺醇体外沉积模式之间的关系。在精密包衣室中,用由分散在异丙醇(IPA)和/或水混合物中的微粉化乳糖组成的液体悬浮液对乳糖载体颗粒进行喷雾包衣。对表面改性的乳糖颗粒进行分级,然后通过激光衍射测定尺寸、图像分析测定形状、扫描探针显微镜测定表面粗糙度。用双级玻璃撞击器测定硫酸沙丁胺醇从药物 - 乳糖混合物中的体外沉积模式,并表示为药物的细颗粒分数和分散性。如扫描探针地形图和载体颗粒的粗糙度值所示,通过精密包衣工艺将细颗粒固定在载体颗粒上是可行的。一般来说,当使用由较高比例IPA组成的喷雾悬浮液时,更多离散的细颗粒沉积在载体表面,并且表面粗糙度更高。发现硫酸沙丁胺醇的细颗粒分数与乳糖的粗糙度之间存在显著相关性。这种体外药物沉积模式与载体微观表面粗糙度之间建立的关系将有助于优化药物向肺部靶向区域的递送。

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