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硝苯地平纳米颗粒团聚作为一种干粉气雾剂的制剂策略。

Nifedipine nanoparticle agglomeration as a dry powder aerosol formulation strategy.

作者信息

Plumley Carl, Gorman Eric M, El-Gendy Nashwa, Bybee Connor R, Munson Eric J, Berkland Cory

机构信息

Department of Chemical and Petroleum Engineering, The University of Kansas, Lawrence, KS 66047, United States of America.

出版信息

Int J Pharm. 2009 Mar 18;369(1-2):136-43. doi: 10.1016/j.ijpharm.2008.10.016. Epub 2008 Oct 25.

Abstract

Efficient administration of drugs represents a leading challenge in pulmonary medicine. Dry powder aerosols are of great interest compared to traditional aerosolized liquid formulations in that they may offer improved stability, ease of administration, and simple device design. Particles 1-5microm in size typically facilitate lung deposition. Nanoparticles may be exhaled as a result of their small size; however, they are desired to enhance the dissolution rate of poorly soluble drugs. Nanoparticles of the hypertension drug nifedipine were co-precipitated with stearic acid to form a colloid exhibiting negative surface charge. Nifedipine nanoparticle colloids were destabilized by using sodium chloride to disrupt the electrostatic repulsion between particles as a means to achieve the agglomerated nanoparticles of a controlled size. The aerodynamic performance of agglomerated nanoparticles was determined by cascade impaction. The powders were found to be well suited for pulmonary delivery. In addition, nanoparticle agglomerates revealed enhanced dissolution of the drug species suggesting the value of this formulation approach for poorly water-soluble pulmonary medicines. Ultimately, nifedipine powders are envisioned as an approach to treat pulmonary hypertension.

摘要

药物的有效给药是肺病医学中的一项主要挑战。与传统的雾化液体制剂相比,干粉气雾剂备受关注,因为它们可能具有更高的稳定性、给药便利性和简单的装置设计。1-5微米大小的颗粒通常有助于肺部沉积。纳米颗粒由于尺寸小可能会被呼出;然而,人们希望它们能提高难溶性药物的溶解速率。高血压药物硝苯地平的纳米颗粒与硬脂酸共沉淀,形成具有负表面电荷的胶体。通过使用氯化钠破坏颗粒之间的静电排斥,使硝苯地平纳米颗粒胶体失稳,以此获得尺寸可控的团聚纳米颗粒。通过级联冲击法测定团聚纳米颗粒的空气动力学性能。发现这些粉末非常适合肺部给药。此外,纳米颗粒团聚体显示出药物的溶解增强,这表明这种制剂方法对于水溶性差的肺部药物具有价值。最终,硝苯地平粉末有望成为治疗肺动脉高压的一种方法。

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