吸入粉雾剂给药装置的研究进展

综述国际上近年来吸入粉雾剂给药装置的研究进展状况,指出我国应加快对微粉化气雾剂药品的研发,尤其应注重对纳米技术在吸入粉雾剂中的应用.     

呼吸道给药的新剂型——粉雾剂

粉雾剂因不含抛射剂及可避免使用时的协同困难而越来越受到人们的重视，并有取代气雾剂的趋势。早在８０年代初国外即已对偻雾剂进行了深入的研究，而国内尚处于起步阶段。本文概述粉雾剂的发展，比较了粉雾剂与氯雾剂优缺点，对组成粉雾剂的药物粉末的处方设计及呼入装置进行了论述，并指出用于吸入疗法的粉雾剂的研究开发应用从三个文献考虑：粉末的雾化、吸入装置的转运性能和病人的肿气产生的雾化能量。     

粉雾剂中乳糖对药物在模拟呼吸道沉降部位的影响

以硫酸沙丁胺醇为模型药物,以休止角为流动性指标。选用双冲程碰撞试验仪,评价乳糖的类型、大小对粉雾剂流动性以及对药物在呼吸道沉降的影响。结果显示,重结晶乳糖休止角较市售乳糖小,并优选其粒径54-100μm的为粉雾剂载体,呼吸道沉降研究结果显示,在各粒径区域,以粒径54-100μm重结晶乳糖为载体的物理混合型粉雾剂在模拟肺部沉降量最大。     

可溶性载体对左旋硫酸沙丁胺醇胶囊型粉雾剂的体外影响

目的：通过对左旋硫酸沙丁胺醇胶囊型粉雾剂可溶性载体的考察,筛选出最佳的载体材料及制备工艺。方法：对于可溶性载体辅料,采用纳米磨与喷雾干燥仪分别制备药物、辅料的颗粒物,测定颗粒的理化性质及肺部有效沉积率。结果：喷雾干燥仪制备后,载体粒径在25.35~52.94 μm之间,其中乳糖外观圆整,粒径为25.35 μm,乳糖的休止角为33.20°,乳糖的含水量最低为0.99%,压缩度为17.68%,有效沉积率为14.21%,符合药典对粉雾剂的要求。结论：喷雾制备的乳糖,其粉体性能良好,是适合左旋沙丁胺醇粉雾剂的载体材料。     

蛋白质和肽类药物结部给药新剂型—吸入粉雾剂

蛋白质和肽类药物的常用制剂生物利用度低,因此开发这类药物的新剂型成为近年来制剂学研究的一个热点。本文综述了蛋白质和肽类药物肺部给药的新剂型－吸入粉雾剂的优点及其新产品、所用载体、物理性能评价指标、吸入装置以及生物利用度。     

吸气流速对载体型粉雾剂分散行为影响的考察

本试验考察了吸入气流大小对以HandiHaler(R)为药物递送装置的载体型粉雾剂中粉末分散、沉积表现的影响.将载体乳糖Lactohale LH206与微粉化马来酸氯苯那敏混合,制得制剂粉末模型,利用新一代撞击器分析制剂粉末在20、30、40、50、60 L/min流速下的分散表现.同时,运用计算流体力学耦合离散元建模...     

气流速度对粉雾剂在呼吸道沉降的影响

目的 :研究吸入速度对不同粒径粉雾剂在呼吸道沉降的影响。方法 :以硫酸沙丁胺醇为模型药物 ,用双冲程试验仪评价不同的气流速度对吸入型粉雾剂在模拟肺部的沉降量。结果 :粒径为 5 4～ 10 0μm的重结晶乳糖为载体的硫酸沙丁胺醇混合型粉雾剂 ,增加吸入速度 ,提高药物在肺部的沉积量 ;而乳糖、甘露醇为载体 ,喷雾干燥法制备的粒径为 0 .5～ 6.5 μm粉雾剂 ,增加吸入速度 ,药物在肺部沉积量基本不变直至下降。结论 :物理混合型吸入剂随气流速度的增加 ,药物在肺部的沉降量增加。含载体喷干型吸入剂 (0 .5～ 6.5 μm)中的药物在肺部的沉降量取决于载体 (如甘露醇 )和吸入速度 (如 3 0 L· min-1 )。     

胰岛素粉雾剂与注射剂治疗2型糖尿病的效果分析

目的：探讨胰岛素粉雾剂治疗2型糖尿病的临床效果。方法选取2012年1月~2014年4月本院收治的120例2型糖尿病患者为研究对象,将患者随机分成观察组与对照组,每组各60例。对照组患者给予胰岛素注射剂皮下注射治疗,观察组患者给予胰岛素粉雾剂吸入治疗,比较两组患者的血糖控制及不良反应的发生情况。结果观察组空腹血糖、餐后2h血糖以及糖化血红蛋白水平较对照组均明显下降,低血糖反应的发生率也明显低于对照组（P〈0.05）。结论胰岛素粉雾剂治疗2型糖尿病不仅能够有效控制患者血糖水平,提高临床效果,还能有效降低低血糖反应的发生率,提高临床治疗的安全性,是临床治疗2型糖尿病的有效药物,值得临床推广应用。     

影响吸入粉雾剂分散性能的制剂因素

综述了影响吸入粉雾剂分散性能的主要制刺因素，简要介绍了近年来提高粉雾剂性能的制剂方法的研究进展和有关研发和评价的新技术。     

干粉吸入剂的有效性及质量评价

综述了影响干粉吸入剂有效性的因素,并对其体内外测定方法及质量控制进行了概述.     

Relative bioavailability of salbutamol to the lung following inhalation via a novel dry powder inhaler and a standard metered dose inhaler

Aims The number of dry powder inhaler (DPI) devices could increase because they are easier to use than a metered dose inhaler (MDI). Using urinary excretion, the relative bioavailability of salbutamol to the lungs and the body for a prototype DPI has been compared with an MDI.
Methods A randomized, double-blind, two way crossover study compared the amount of salbutamol in the urine 30  min following inhalation of 2×100  μg salbutamol from a prototype DPI (Innovata Biomed Ltd, UK) and a Ventolin^® (Allen and Hanburys Ltd, UK) MDI in 10 volunteers. The amount of salbutamol and its metabolite, the ester sulphate conjugate, renally excreted up to 24  h post inhalation was also determined to evaluate the relative bioavailability of salbutamol to the body.
Results The mean (s.d.) 30  min post-treatment urinary excretion for the prototype DPI and MDI was 8.4 (2.6) and 5.0 (1.9)  μg, respectively ( P <0.001). The total amount of salbutamol and its ester metabolite excreted in the urine over the 24  h period after inhalation was 187.9 (77.6) and 137.6 (40.0)  μg ( P <0.05).
Conclusions The prototype DPI delivered more salbutamol to the body and the lungs than a conventional MDI. This finding supports further development of the prototype DPI. The urinary salbutamol method is able to discriminate between two different inhalation systems.     

Optimization of a dry powder inhaler of ciprofloxacin-loaded polymeric nanomicelles by spray drying process

Ciprofloxacin is a commonly prescribed antibiotic for treatment of pulmonary infections. Nanocarriers such as nanomicelles can increase the drug residence time in the lungs and enhance their antibacterial effects. Dry powder inhalers (DPIs) are the preferred pulmonary drug delivery system and preparation of an optimum nanoaggregate from nanomicelles by means of spray drying would be valuable. The two-level full factorial design was performed in 16 runs. The effects of carrier type, anti-adhesion agent type, carrier to nanoparticle ratio and anti-adhesion agent to carrier ratio on the size of the microparticles, their in vitro pulmonary deposition, and redispersibility were investigated. Its antibacterial effects against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Streptococcus pneumoniae also were investigated. All independent variables were fitted into two-factorial interaction models. The optimum nanoaggregate was prepared using mannitol and L-phenylalanine with a D_0.5 of 1.7?µm and 60% fine particles. The process had no negative effect on the stability or drug release profile of the nanomicelles. The antibacterial effects of ciprofloxacin against microorganisms increased significantly. This spray drying process could be used for preparation of an optimum DPI from polymeric nanomicelles. This formulation could increase the efficacy of ciprofloxacin for treatment of pulmonary infections.     

影响干粉吸入剂肺沉积的制剂因素

干粉吸入剂的制剂因素包括药物粉末的处方组成、给药装置类型等,是影响药物肺沉积的主要因素。文中按照药物处方组成将干粉吸入剂分成无载体、药物-载体、药物-添加剂、药物-载体-添加剂4种类型,并分别对其影响肺沉积的制剂因素进行了分析。     

Low density,good flowability cyclodextrin-raffinose binary carrier for dry powder inhaler: anti-hygroscopicity and aerosolization performance enhancement

Background: The hygroscopicity of raffinose carrier for dry powder inhaler (DPI) was the main obstacle for its further application. Hygroscopicity-induced agglomeration would cause deterioration of aerosolization performance of raffinose, undermining the delivery efficiency.

Methods: Cyclodextrin-raffinose binary carriers (CRBCs) were produced by spray-drying so as to surmount the above issue. Physicochemical attributes and formation mechanism of CRBCs were explored in detail. The flow property of CRBCs was examined by FT4 Powder Rheometer. Hygroscopicity of CRBCs was elucidated by dynamic vapor sorption study. Aerosolization performance was evaluated by in vitro deposition profile and in vivo pharmacokinetic profile of CRBC based DPI formulations.

Results: The optimal formulation of CRBC (R₄) was proven to possess anti-hygroscopicity and aerosolization performance enhancement properties. Concisely, the moisture uptake of R₄ was c.a. 5% which was far lower than spray-dried raffinose (R₀, c.a. 65%). R₄ exhibited a high fine particle fraction value of 70.56 ± 0.61% and it was 3.75-fold against R₀. The pulmonary and plasmatic bioavailability of R₄ were significantly higher than R₀ (p < 0.05).

Conclusion: CRBC with anti-hygroscopicity and aerosolization performance enhancement properties was a promising approach for pulmonary drug delivery, which could provide new possibilities to the application of hygroscopic carriers for DPI.     

干粉吸入剂的粉末定量分装设备浅析

干粉吸入剂是一种新兴呼吸道给药剂型,其吸入粉末的分装装置不同于常见的口服固体粉末分装装置。本文综述国际上常用的干粉吸入剂的粉末定量分装装置,包括标准定量器装置装置、真空滚筒分装装置、Xcelodose精确粉末微定量装置等,同时介绍几种较新的、处于研发阶段的粉末分装装置。     

Rational design of a dry powder inhaler: device design and optimisation

Objectives As part of the development of a dry powder inhalation system for the treatment of asthma and chronic obstructive pulmonary disease, this work specifically aimed at the systematic, however, cost-effective and efficient development of an inhalation device. Methods Based on theoretical design considerations and an initial inhaler prototype, the concept of a modular inhaler was developed. The modular inhaler was used for the systematic evaluation of the influence of the inhaler's inner dimensions on the resistance to the air flow and the in-vitro deposition characteristics of the inhalation system by using statistical design of experiments and cascade impaction analysis. Key findings A reliable statistical model enabled the accurate prediction of the device resistance of any combination of inner dimensions of the inhaler. In conjunction with results from in-vitro deposition studies, this allowed for the definition of optimised inner dimensions of the inhaler to maximise the fine particle fraction and minimise oropharyngeal deposition within the desired range of the inhaler's resistance to air flow. Conclusions The concept of the modular inhaler and statistical design and evaluation of experiments proved to be important tools for an efficient and successful product development. Eventually, the approaches described and the knowledge obtained enabled the cost-effective development and design of a technically feasible and competitive dry powder inhaler.     

The rejuvenated pressurised metered dose inhaler

The pressurised metered-dose inhaler (pMDI) has now been available for 50 years. Once regarded as an inefficient and difficult-to-use device, the technology has evolved significantly over the last few years, particularly since the introduction of novel formulations containing hydrofluoroalkane (HFA) propellants. Many modern HFA pMDIs deposit drug more efficiently in the lungs, impact less forcefully on the back of the throat and feel less cold than their chlorofluorocarbon pMDI counterparts. An improved understanding of technical factors makes it possible to design HFA pMDIs to have specific spray properties, particularly in terms of fine particle dose and spray velocity. Device technology has also progressed with the introduction of compact and convenient breath-actuated, breath-coordinated and velocity-modifying devices, which help patients to achieve a reliable lung dose. Although it faces competition from dry powder inhalers and possibly from novel soft-mist inhalers containing liquid formulations, the rejuvenated HFA pMDI is a device with a significant future for asthma, chronic obstructive pulmonary disease and wider treatment indications.