Feasibility of a High-Dose Inhaled Indomethacin Dry Powder with Dual Deposition for Pulmonary and Oral Delivery.

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Jamie E Spahn, Amr Hefnawy, Feng Zhang, Hugh D C Smyth
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Abstract

In this study we have developed a high-dose dry powder inhaler formulation of indomethacin using a novel approach to carrier-based formulations. Specifically, larger drug particles serve as the carrier for the smaller micronized drug particles, such that an inhaled dose is combined with an oral dose. To study this system, the aerosol performance of a standard indomethacin-lactose formulation was compared to carrier-free micronized indomethacin and a drug-as-carrier formulation (a micronized indomethacin-coarse indomethacin blend). Indomethacin with lactose showed a very poor aerosol performance, indicating high adhesion between the drug and carrier. The performance of the carrier-free micronized drug was significantly better, indicating low cohesion. Coarse drug particles as a carrier allowed improved powder flow and aerosol performance while also providing a potential secondary route of absorption of indomethacin, namely oral. An optimal formulation ratio of 1:1 (w/w) fine indomethacin-coarse indomethacin was developed in this study.

大剂量吸入式吲哚美辛干粉在肺部和口腔双重沉积的可行性。
在这项研究中,我们采用一种基于载体的新型制剂方法,开发出了吲哚美辛的大剂量干粉吸入剂制剂。具体来说,较大的药物颗粒作为较小的微粉化药物颗粒的载体,使吸入剂量与口服剂量相结合。为了研究这种系统,我们将吲哚美辛-乳糖标准配方的气溶胶性能与不含载体的微粉化吲哚美辛和以药物为载体的配方(微粉化吲哚美辛-粗吲哚美辛混合物)进行了比较。含乳糖的吲哚美辛气溶胶性能很差,表明药物和载体之间的粘附性很高。而不含载体的微粉化药物的性能要好得多,这表明它们之间的粘附性很低。粗药物颗粒作为载体可以改善粉末流动性和气溶胶性能,同时还提供了吲哚美辛的潜在二次吸收途径,即口服。本研究开发出了吲哚美辛-粗吲哚美辛 1:1(重量比)的最佳配方比例。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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