呼吸道药物递送——雾化吸入剂的研究进展

吸入给药是防治哮喘、慢性阻塞性肺疾病(COPD)等呼吸道疾病的首选给药方式.常见的吸入给药制剂包括压力定量吸入剂、干粉吸入剂和雾化吸入剂.与前两者相比,雾化吸入剂具有处方简单、剂量灵活性好、吸入效果受吸气模式影响较小等特点.并在最近十几年里取得了快速发展,由过去仅在医院使用逐渐向便携化、智能化发展.本文就目前几种主要雾...     

肺部吸入给药制剂及临床应用

目的:分析和综述肺吸入制剂的分类、现状及其临床用药。方法:收集国内外发表出版的相关论文及专著,对肺部吸入给药的特点及临床药物制剂进行了分析总结。结果与结论:肺部吸入给药是防治哮喘、慢性阻塞性肺病等呼吸道疾病的首选给药方式。常见的吸入给药制剂包括定量吸入气雾剂、干粉吸入剂和雾化吸入剂,所用药物主要为β2受体激动剂、抗胆碱药物、吸入性糖皮质激素及复方药物等。     

影响干粉吸入剂雾化和沉积性能的制剂因素

干粉吸入剂是近年来肺部给药制剂研发的热点。随着微粉化技术不断成熟,新型给药装置日益涌现,干粉吸入剂的应用范围越来越广。本文从微粉化的药物、载体和干粉吸入器等3个方面综述了干粉吸入剂的处方组成,并重点介绍了影响药物粉末雾化和沉积性能的几个关键因素。     

肺内吸入给药治疗哮喘和慢性阻塞性肺病研究进展

哮喘和慢性阻塞性肺疾病(COPD)是最常见的呼吸道疾病之一,全球分别有3 亿和2.1 亿患者。肺部吸入给药是治疗和管理哮喘、COPD 等呼吸道疾病的首选给药方式,而患者的依从性与该类制剂的疗效优劣有密切关系。综述现在已经上市的肺部吸入给药治疗哮喘和慢性阻塞性肺疾病的主要剂型和药品,以及雾化吸入剂、定量吸入剂和干粉吸入剂对患者依从性的影响,并认为提高患者依从性需要反复提供给患者个性化用药和正确使用给药装置的指导。     

肺部吸入制剂评价方法研究进展

肺部吸入制剂在治疗肺炎、哮喘、慢性阻塞性肺病（COPD）等肺部疾病中的应用广泛。肺部吸入制剂主要包括吸入气雾剂、干粉吸入剂、吸入喷雾剂和吸入溶液,其体外评价方法主要包括递送剂量及递送剂量均一性,空气动力学粒径分布,喷雾模式和喷雾形态;体内评价方法主要包括药动学研究与放射性核素成像。就肺部吸入制剂的体内外评价方法的研究进展进行综述。     

吸入给药七步法的改进及其效果

目的：探讨改进后的吸入给药法在指导吸入剂正确使用中的应用效果。方法：将吸入给药七步法改进为给药十步法,并应用于对本院2018年1~12月使用吸入剂患者进行装置使用指导,以吸入剂的操作评分和使用正确率作为衡量标准,对比干预前后患者吸入剂操作情况的变化。结果：干预前患者吸入剂操作评分为5.6分,装置使用正确率为27.1%,经过3次干预后,吸入剂操作评分分别为7.3分、8.0分、8.2分,装置使用正确率分别为49.5%、 64.4%、73.2%,吸入给药十步法指导干预后,吸入剂操作评分提高了45.8%,装置使用正确率提高了2.7倍。结论：改进后的十步法指导吸入剂应用,提高了使用装置的正确率,该法步骤明确、易理解,易掌握。     

阿奇霉素干粉吸入剂的制备及稳定性考察

摘要：目的:制备阿奇霉素干粉吸入剂并考察其稳定性。方法:采用气流粉碎法制备阿奇霉素干粉吸入剂,以粉末收率、粒子空气动力学粒径、休止角和阿奇霉素干粉吸入剂的细微粒子剂量为考察指标,通过正交设计结合多指标综合评价法优化最佳制备工艺,并考察阿奇霉素干粉吸入剂的稳定性。结果:通过正交试验-多指标综合评价,最佳制备工艺为:分选频率25Hz;进料量80 g;粉碎次数1次;粉碎压力1.0 MPa。在稳定性考察中阿奇霉素干粉吸入剂的各项指标在观察期内无明显变化。结论:所制备的阿奇霉素干粉吸入剂适合肺部吸入给药,且具有较好的稳定性。     

干粉吸入剂中粉末特性及其评价

干粉吸入剂利用肺部给药途径的优越性，克服了气雾剂定量吸入的种种缺点，广泛应用于肺部呼吸道疾病的治疗，也为大分子多肤类药物开辟了新的给药途径。本文就干粉吸入剂中粉末的大小、形态、流动性和吸湿性等特性进行了综述。     

雾化吸入法在临床中应用的研究进展

雾化吸入是利用雾化器将药物制成微小雾粒,使之吸入呼吸道,以达到消炎、祛痰、平喘等作用的给药方式,具有吸收面积大,起效迅速,不良反应少等优点,已成为治疗呼吸系统疾病最安全、有效的给药方法之一。雾化吸入治疗呼吸系统疾病在临床上已应用多年且成效显著。近年来有大量研究表明,雾化吸入治疗一些非呼吸系统疾病也有不错的疗效,而且不同雾化方式治疗相同疾病时产生的效果有较大的差异。故本文就雾化吸入器的种类、不同雾化方式的效果差异、雾化吸入治疗疾病的类别以及中药制剂的雾化吸入等方面加以综述,为完善中药雾化吸入剂的评价体系和制定临床雾化吸入操作标准提供一定的依据与参考。     

新型肺部给药系统-吸入粉雾剂

吸入粉雾剂 (又名粉雾吸入剂、干粉吸入剂、粉雾剂) 是一种新型的肺部给药系统, 具有稳定性好, 不含抛射剂氟里昂等优点, 近年来受到人们的广泛关注。粉雾剂由粉末吸入装置和供吸入用的干粉组成。本文就近年来粉雾剂的研究进展, 包括吸收机制, 粉雾剂品种, 吸入装置, 制备技术和评价特征参数等进行了综述。     

Development and Performance Evaluation of a High-Volume Ultrafine Particle Concentrator for Inhalation Toxicological Studies

This article presents the development and performance evaluation of a high-volume ultrafine particle concentrator. The ultrafine particle concentrator consists of several units, including a size-selective inlet; a condensational growth unit; a series of two virtual impactors (concentrators); a thermal size restoration device; an air cooler; and a size-selective outlet. Ambient ultrafine particles are condensationally grown to supermicrometer sizes and then are concentrated by a factor of 40 to 50 using a two-stage virtual impactor. Subsequently, ultrafine particle size distribution is restored, using a thermal method. The Harvard ultrafine concentrated ambient particle system (HUCAPS) delivers 58 lpm of concentrated aerosol that can be used for in vivo or in vitro inhalation toxicological studies. Overall, pressure drop through the system is only 2.2 kPa, which is adequately low for inhalation toxicological exposure tests. The performance of this system was evaluated using single-component artificial aerosols with a variety of physicochemical properties as well as ambient air. These experiments showed that for an optimum supersaturation ratio of 3.0, all ultrafine particles grow and get concentrated by about the same enrichment factor, regardless of their composition and surface properties.     

Development and performance evaluation of a high-volume ultrafine particle concentrator for inhalation toxicological studies

This article presents the development and performance evaluation of a high-volume ultrafine particle concentrator. The ultrafine particle concentrator consists of several units, including a size-selective inlet; a condensational growth unit; a series of two virtual impactors (concentrators); a thermal size restoration device; an air cooler; and a size-selective outlet. Ambient ultrafine particles are condensationally grown to supermicrometer sizes and then are concentrated by a factor of 40 to 50 using a two-stage virtual impactor. Subsequently, ultrafine particle size distribution is restored, using a thermal method. The Harvard ultrafine concentrated ambient particle system (HUCAPS) delivers 58 lpm of concentrated aerosol that can be used for in vivo or in vitro inhalation toxicological studies. Overall, pressure drop through the system is only 2.2 kPa, which is adequately low for inhalation toxicological exposure tests. The performance of this system was evaluated using single-component artificial aerosols with a variety of physicochemical properties as well as ambient air. These experiments showed that for an optimum supersaturation ratio of 3.0, all ultrafine particles grow and get concentrated by about the same enrichment factor, regardless of their composition and surface properties.     

The characterisation of inhalation devices by an inhalation simulator: The Electronic Lung.

The Electronic Lung is an inhalation simulator designed for the characterisation of breath-actuated inhalation devices. It enables the in-vitro evaluation of devices under conditions that have been produced in-vivo. Data generated on the Serevent Diskhaler inhaler have highlighted the reproducibility of particle size distribution of drug delivered from the device over a range of inhalation parameters.     

利巴韦林脂质体吸入粉雾剂的研制与初步评价

目的 为解决利巴韦林存在的明显不良反应问题,研制利巴韦林脂质体吸入粉雾剂,并初步评价其质量特性。方法 采用薄膜分散法制备利巴韦林脂质体,再冻干制备成利巴韦林脂质体粉雾剂,并考察制剂的外观形态、流动性、松密度、包封率、复溶液粒径、聚合物分散指数、电位及亲水性。结果 利巴韦林脂质体粉雾剂形态、粒径、电位、流动性与亲水性均较好,能满足粉雾剂給药的基本要求。结论 应用该方法制备利巴韦林脂质体粉雾剂的制剂技术是可行的,为后续体内外研究提供制剂学技术依据。     

纳米晶体技术在肺吸入给药中的研究进展

肺吸入给药是可实现肺靶向或全身给药的理想给药途径。然而肺部结构特征的复杂性给开发肺吸入制剂研发带来了困难,纳米晶体技术为解决难溶性药物肺部给药提供了一种有效的方法,其粒径小,可克服肺部中存在的生理屏障,提高药物的生物利用度,近年来引起了药物制剂学家的广泛关注。本文围绕肺部给药的屏障及纳米晶体在肺吸入给药的应用展开综述,期望为促进难溶性药物肺部给药提供借鉴。     

Mass output and particle size distribution of glucocorticosteroids emitted from different inhalation devices depending on various inspiratory parameters.

Efficient inhalation therapy depends on successful delivery of the drug to the lung. The efficacy of drug delivery is not only influenced by the characteristics of the inhalation device, but also by the patient's handling of the device and by the inspiratory maneuver achieved through the device. We analyzed the output characteristics of three different chlorofluorocarbon (CFC)-free breath-actuated inhalers for inhaled glucocorticosteroids (BUD Turbohaler, FP Diskus/Accuhaler and HFA-BDP Autohaler, respectively). Mass output and particle size distribution of drug aerosol delivered by the inhalers were determined depending on different inhalation parameters in vitro using an Andersen cascade impactor. We found that, beside the peak inspiratory flow (PIF), other factors such as flow acceleration and inhalation volume also have significant effects on aerosol generation with respect to mass output and particle size distribution. Thus, these parameters should be taken into account when a suitable device for an individual patient is to be selected. The dependency on inspiratory parameters was most pronounced for the dry powder inhalers. The Turbohaler showed by far the highest variance in particle output (fine particle fraction ranging from 3.4% to 22.1% of label claim), whereas the Diskus was less dependent on variations in inhalation (10.6% to 18.5% of label claim). The most constant aerosol output was found for the Autohaler, which also released the highest fine particle fraction (43.1% to 56.6% of label claim).     

Clinical perspectives on pulmonary systemic and macromolecular delivery

The large epithelial surface area, the high organ vascularization, the thin nature of the alveolar epithelium and the immense capacity for solute exchange are factors that led the lung to serve as an ideal administration route for the application of drugs for treatment of systemic disorders. However, the deposition behaviour of aerosol particles in the respiratory tract depends on a number of physical (e.g. properties of the particle), chemical (e.g. properties of the drug) and physiological (e.g. breathing pattern, pulmonary diseases) factors. If these are not considered, it will not be possible to deposit a reproducible and sufficient amount of drug in a predefined lung region by means of aerosol inhalation. The lack of consideration of such issues led to many problems in inhalation drug therapy for many years mainly because physiological background of aerosol inhalation was not fully understood. However, over the last 20 years, there has been considerable progress in aerosol research and in the understanding of the underlying mechanisms of particle inhalation and pulmonary particle deposition. As a consequence, an increasing number of studies have been performed for the lung administration of drugs using a variety of different inhalation techniques. This review describes the physical and in part some of the physiological requirements that need to be considered for the optimization of pulmonary drug delivery to target certain lung regions.     

吸入用乙酰半胱氨酸溶液雾化特性的体外评价

目的 研究吸入用乙酰半胱氨酸溶液的雾化特性,建立体外评价方法。方法 使用呼吸模拟装置对吸入用乙酰半胱氨酸溶液的递送速率和递送总量进行研究,使用新一代药用多级撞击器（NGI）测定空气动力学粒径分布。结果 不同雾化装置检测递送速率和递送总量数据存在明显差异,但使用同品牌雾化装置时吸入用乙酰半胱氨酸溶液自制样品和参比制剂的递送速率和递送总量无明显差异。不同雾化装置检测空气动力学粒径分布数据存在明显差异,但是使用同一品牌雾化装置,吸入用乙酰半胱氨酸溶液自制样品与参比制剂无明显差异。结论 所测定的体外数据描述了吸入用乙酰半胱氨酸溶液的体外特征,可为该制剂的体外评价提供参考。     

Drug absorption from inhalation aerosols administered by positive-pressure ventilation. I: Administration of a characterized, solid disodium fluorescein aerosol under a controlled respiratory regime to the beagle dog

An apparatus and novel method is described for administration of well-characterized inhalation aerosols, under strictly controlled respiratory regimes, direct to the respiratory tract (RT) of the beagle dog by positive-pressure ventilation. The method enables the study of systemic absorption kinetics of compounds delivered as inhalation aerosols as a function of the aerosol particle size and respiratory variables provided their intrinsic pharmacokinetics are linear. Aerosol characteristics are determined by sampling the aerosol at a point close to its entry to the endotracheally intubated animal. The chosen positive-pressure ventilatory regime, which is monitored as airway pressure and exhaled volume versus time, can be held constant for the aerosol administration period. The methodology is illustrated by administration of a solid polydispersed aerosol of disodium fluorescein. Resultant plasma concentrations (C) were determined as a function of time by sampling from an indwelling venous cannula. The pharmacokinetic analysis of resultant C versus time data, together with that from an intravenous control experiment, is described to determine the amount absorbed as a function of time. Following aerosol administration according to the chosen respiratory regime, fluorescein was rapidly absorbed from the RT. The methodology will enable systematic variation of the particle size and positive-pressure respiratory regime in order to determine effects on drug absorption kinetics.