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含利福平的可吸入多孔微粒的制备、体外表征及体内药代动力学评价

Preparation, in vitro characterization, and in vivo pharmacokinetic evaluation of respirable porous microparticles containing rifampicin.

作者信息

Kundawala Aliasgar, Patel Vishnu, Patel Harsha, Choudhary Dhaglaram

机构信息

Indukaka Ipcowala College of Pharmacy, New Vallabh Vidyanagar, Dist. Anand (Gujarat) - 388121, India.

A. R. College of Pharmacy and G H Patel Institute of pharmacy, Vallabh Vidyanagar, Dist. Anand (Gujarat) - 388120, India.

出版信息

Sci Pharm. 2014 Jul 23;82(3):665-81. doi: 10.3797/scipharm.1307-03. Print 2014 Jul-Sep.


DOI:10.3797/scipharm.1307-03
PMID:25853075
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4318219/
Abstract

This study aimed to prepare and evaluate rifampicin microparticles for the lung delivery of rifampicin as respirable powder. The microparticles were prepared using chitosan by the spray-drying method and evaluated for aerodynamic properties and pulmonary drug absorption. To control the drug release, tripoly-phosphate in different concentrations 0.6, 0.9, 1.2, and 1.5 was employed to get a sustained drug release profile. The microparticles were evaluated for drug loading, % entrapment efficiency, tapped density, morphological characteristics, and in vitro drug release studies. Aerosol properties were determined using the Andersen cascade impactor. Porous microparticles with particle sizes (d0.5) less than 10 μm were obtained. The entrapment of rifampicin in microparticles was up to 72%. In vitro drug release suggested that the crosslinked microparticles showed sustained release for more than 12 hrs. The drug release rate was found to be decreased as the TPP concentration was increased. The microparticles showed a fine particle fraction in the range of 55-63% with mass median aerodynamic diameter (MMAD) values below 3 μm. The in vivo pulmonary absorption of the chitosan microparticles suggested a sustained drug release profile up to 72 hrs with an elimination rate of 0.010 per hr. The studies revealed that the spray-dried porous microparticles have suitable properties to be used as respirable powder in rifampicin delivery to the lungs.

摘要

本研究旨在制备并评估用于肺部递送利福平的可吸入粉末状利福平微粒。采用壳聚糖通过喷雾干燥法制备微粒,并对其空气动力学性质和肺部药物吸收进行评估。为控制药物释放,使用不同浓度(0.6、0.9、1.2和1.5)的三聚磷酸钠以获得持续的药物释放曲线。对微粒进行药物负载、包封率、振实密度、形态特征和体外药物释放研究评估。使用安德森撞击器测定气溶胶性质。获得了粒径(d0.5)小于10μm的多孔微粒。利福平在微粒中的包封率高达72%。体外药物释放表明交联微粒显示出超过12小时的持续释放。发现随着三聚磷酸钠浓度的增加,药物释放速率降低。微粒的细颗粒分数在55 - 63%范围内,质量中值空气动力学直径(MMAD)值低于3μm。壳聚糖微粒的体内肺部吸收表明持续药物释放曲线长达72小时,消除速率为每小时0.010。研究表明,喷雾干燥的多孔微粒具有适合用作将利福平递送至肺部的可吸入粉末的性质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/bef304b37959/f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/d4ed6408607d/f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/0cfae71f1143/f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/c0c655a04196/f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/ce0f3f68ca24/f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/e7399b28c74f/f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/d4ed6408607d/f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/98a6f81b019c/f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/bef304b37959/f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/d4ed6408607d/f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/0cfae71f1143/f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/c0c655a04196/f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/ce0f3f68ca24/f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/e7399b28c74f/f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/d4ed6408607d/f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/98a6f81b019c/f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a55/4318219/bef304b37959/f0008.jpg

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本文引用的文献

[1]
Composition influence on pulmonary delivery of rifampicin liposomes.

Pharmaceutics. 2012-11-27

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