高剂量吸入性吲哚美辛干粉双重沉积用于肺部和口服给药的可行性

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

作者信息

Spahn Jamie E, Hefnawy Amr, Zhang Feng, Smyth Hugh D C

机构信息

Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX 78712, USA.

出版信息

Pharmaceutics. 2024 Sep 28;16(10):1269. doi: 10.3390/pharmaceutics16101269.

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 (/) fine indomethacin-coarse indomethacin was developed in this study.

摘要

在本研究中,我们采用一种基于载体剂型的新方法,开发了一种高剂量的吲哚美辛干粉吸入剂配方。具体而言,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。为了研究该系统,将标准吲哚美辛 - 乳糖配方的气雾剂性能与无载体微粉化吲哚美辛和药物作为载体的配方(微粉化吲哚美辛 - 粗吲哚美辛混合物)进行了比较。吲哚美辛与乳糖的气雾剂性能非常差,表明药物与载体之间的粘附性很高。无载体微粉化药物的性能明显更好,表明内聚力较低。粗药物颗粒作为载体可改善粉末流动性和气雾剂性能,同时还提供了吲哚美辛潜在的次要吸收途径,即口服。本研究开发了1:1(/)细吲哚美辛 - 粗吲哚美辛的最佳配方比例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdf8/11510369/78d8418fb18c/pharmaceutics-16-01269-g0A1.jpg

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