肺部吸入给药系统的研究进展

肺部给药系统具有起效快、疗效好、同时减少不良反应等优点,已成为一种倍受关注的给药方式.在全球新型给药系统药物市场中,肺部吸入给药系统占有极为重要的地位,特别是在慢性阻塞性肺病和哮喘等与呼吸道相关疾病的治疗方面具有广泛的临床应用价值.本文将从吸入制剂的最新分类、美国FDA已上市产品情况和创新性产品研究进展等方面入手,对目...     

吸入粉雾剂产业化过程中的质量控制

吸入制剂尤其是吸入粉雾剂结构和功能的特殊性,决定其在产业化过程中质量控制的特异性。讨论吸入粉雾剂产业化过程中原辅料、包材、中间体、终产品及稳定性考察过程中的质量控制特异性考察项目及标准设定。     

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。     

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。     

论中药制剂在肿瘤治疗中的优势

现代研究认为 ,肿瘤发病是个多病因、多阶段、多基因的长期过程[1] 。中医对肿瘤发病的认识散见于历代各家论述 ,总体认为是瘤气结核 ,五脏不合 ,九窍不通 ,气血逆乱 ,摄生失宜 ,加之脏腑正气虚损 ,复因情志所伤而诱发肿瘤 ,上述立论 ,肿瘤发病无论是中医理论或西医观点 ,均认为是多方面原因引起。对肿瘤治疗强调突出“早”治。西医的早治是早发现、早手术摘除 ,其次是放化疗。中医的早治是根据肿瘤发病部位 ,内服药物在扶正祛邪 ,软坚散结的基础上加入引经药或在浅表部位外敷 ,以扶其正气 ,散其邪表。根据历年来中西医治疗肿瘤的情况 ,笔者…     

吸入粉雾剂工程颗粒技术研究

对于吸入粉雾剂来说,由于活性药物成分（API）较小的粒径和较高的表面能,导致微粉易于团聚,难以分散。微粒间的内聚力和微粒与乳糖间的粘附力导致粉雾剂产品较低的微细粒子比例（FPF）。通过工程颗粒可以改善API微粒的物化性质,进而显著提高DPI产品的递送效率。概述通过工程颗粒的制备API微粉的方法,包括反溶剂结晶、湿法粉碎/研磨、喷雾/冷冻干燥、超临界流体等方法,可以显著提高粉雾剂的雾化性能。     

吸入粉雾剂产品的开发要点

吸入粉雾剂是药械组合药品,制剂和装置共同决定了产品的质量和雾化性能。在装置的开发中,需要关注使用装置的类型,与制剂处方联合开发;在制剂开发中,要关注粉体的粒度分布、颗粒形态、流动性、比表面积、多晶型及结晶度,提高对物化性质的认识。在产品的检测中,不仅要关注质量标准的检测项目,还要从患者的角度出发考察产品的雾化性能,以满足不同患者的使用。从装置的开发、制剂处方的研发以及质量控制3个方面阐述了吸入粉雾剂产品开发中需要重点关注的内容,以提高粉雾剂产品研发速度和质量。     

FDA吸入制剂仿制药开发特定药品指导原则汇总分析

通过梳理美国FDA发布的34个吸入制剂仿制药开发特定药品指导原则,总结了吸入粉雾剂、吸入气雾剂、吸入喷雾剂、吸入混悬液和吸入溶液仿制药开发所用的体外生物等效性研究、药动学研究、药效学研究、临床终点研究和装置比较方法,比较了各品种开发方法、试验设计、主要研究终点和等效性标准方面的差异,为吸入制剂仿制药开发提供更有针对性的...     

儿童哮喘吸入制剂及相关装置临床应用新进展

吸入制剂是指原料药物溶解或分散于合适介质中,以蒸气或者气溶胶形式进入到肺部发生局部或者全身作用的液体或固体制剂。吸入装置是将药物分散成小雾滴或小液滴作用至肺部的装置。本文通过介绍儿童哮喘雾化吸入药物的种类、临床疗效、和吸入装置的原理、特点、临床应用等为医护人员、医药、制剂公司提供参考。     

吸入粉雾剂的喷雾工艺及表征研究进展

吸入粉雾剂是改善肺部疾病治疗的研究热点,具有上市产品多、生产工艺成熟、颗粒影响因素多、晶型转化因素多、颗粒表面物性变化等特点.目前,吸入粉雾剂存在产品效用、贮藏及生产工艺因素的关联研究不系统等问题,本文对近年来肺部吸入粉雾剂制备新技术(喷雾冷冻干燥技术、微流控-喷雾技术、模板打印技术)及粉体颗粒物理化学表征新技术(反向...     

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。     

纳米粒在干粉吸入剂上的应用进展

介绍纳米粒在干粉吸入剂上的应用进展,分析纳米粒应用于干粉吸入剂上的优势,并结合实例较为系统地介绍供吸入的大粒径中空纳米聚集体的制备方法及形成机制。喷雾干燥法可制备供吸入的大粒径中空纳米聚集体,其形成机制可通过扩散特性参数Peclet数来解释。由于纳米粒在肿瘤靶向性方面的优势和大粒径中空粒子优良的沉积性能,大粒径中空纳米聚集体在干粉吸入剂上具有独特的优势。     

鲑降钙素吸入粉雾剂的制备及其药剂学性质研究鲑降钙素吸入粉雾剂的制备及其药剂学性质研究

目的喷雾干燥法制备鲑降钙素吸入粉雾剂,考察其主要药剂学特性。方法按中国药典2000年版方法测定鲑降钙素吸入粉雾剂排空率及有效部位沉积量,扫描电镜观察粉粒的形态,激光粒度测定仪测定粉粒的粒径大小及分布,差热分析及X射线粉末衍射考察吸入粉雾剂载体的晶型。结果有效部位鲑降钙素沉积量均在10%以上,排空率均在90%以上;相对湿度在52%以下,粉粒呈圆整的分散状态;当RH=75%时粉粒发生较多的粘连和聚集;粉体平均粒径为1.67 μm;差热分析结果显示:吸入粉雾剂中L-亮氨酸的熔融热较单一组分在喷雾干燥后显著下降;X射线粉末衍射图谱中,吸入粉雾剂载体的衍射峰强度较喷雾干燥前显著下降。结论在鲑降钙素吸入粉雾剂载体系统中加入甘露醇,粉粒圆整,加入L-亮氨酸可形成超低密度载体;扫描电镜的结果提示,应严格控制吸入粉雾剂贮存时环境的湿度;喷雾干燥复合载体更有助于无定形的形成。     

Microparticles of rifampicin: comparison of pulmonary route with oral route for drug uptake by alveolar macrophages,phagocytosis activity and toxicity study in albino rats

Abstract

Context: Tuberculosis (TB) is a chronic infectious disease with increasing incidence of drug resistance. Oral treatment for TB and multidrug resistance (MDR)-TB can have serious side effects. The causative agent of TB, Mycobacterium tuberculosis, resides in alveolar macrophages (AM). Pulmonary administration of anti-TB drugs can help in delivery of high concentration to AM. The ability of AM to phagocytose can also be utilized to generate mycobactericidal nitric oxide (NO) to improve efficacy of anti-TB drugs.

Objective: To compare the uptake of rifampicin (RIF) by AM post oral and pulmonary administration of RIF microparticles (RM) and to compare hepatotoxicity and phagocytosis activity.

Materials and Methods: RM were produced by spray drying process. RM were administered to rats through oral as well as intratracheal route. The uptake of RIF by AM and liver was measured. NO was measured in bronchoalveolar lavage (BAL) fluid. SGOT and SGPT levels were measured in serum.

Results: Significantly higher (p?<?0.05) concentration of RIF was found in AM post intratracheal administration. NO production was also significantly higher but less than toxic level. SGOT and SGPT levels as well as uptake of RIF by liver were indicative of no hepatotoxicity post intratracheal administration.

Discussion: Phagocytosis of RM post intratracheal administration leads to significantly higher drug level in AM as well as production of significantly higher levels of NO.

Conclusion: The administration of RM as dry powder inhalation (DPI) formulation may reduce treatment time of TB and chances of drug resistance TB.     

吸入粉雾剂中静电作用的影响因素概述

应用于吸入粉雾剂（DPI）的药物活性成分通常是小粒径绝缘体,容易在制备与运输过程中携带电荷,增加药物之间以及药物-载体之间的黏附性,影响药物在肺部的沉积。了解DPI中粘性粉末静电作用的影响因素是至关重要的,影响因素包括粉末的电阻率、粒度分布、晶习、晶型、引湿性、环境因素、制备条件以及储存条件等。还探讨了静电力对DPI药物含量均一性、递送剂量、原料药与载体的黏附/解吸附能力以及药物在呼吸道的沉积行为的影响。对静电力的认知与理解有助于DPI产品的安全性、质量以及临床有效性的提高。     

Making large,flowable particles of protein or disaccharide in a mini-scale spray dryer

A mini-scale spray dryer, the ProCept 4M8, with a 1.4?m or 2.1?m drying chamber length has been used to prepare large, flowable particles of catalase, trehalose or lactose. A 25?kHz ultrasonic nozzle or a Rayleigh breakup mono-disperse droplet generator was used for atomization. The ultrasonic nozzle produced dried particles of average diameter ≥30?µm that show incipient flow behavior when measured with the vibrating spatula method. A high solute concentration of 69% w/w in the liquid feed was required, which is readily achievable with trehalose but not with the viscous catalase solution. At lower solute concentrations, e.g. 20% w/w, the mono-disperse droplet generator was able to produce well flowable particles of approximately 50?µm diameter, although with a low yield. This is a result of collisions between the droplets falling through the drying chamber when then coalesce. It is possible to produce dried, flowable particles in milligram quantities on a mini-scale spray dryer such as the ProCept using the 25?kHz ultrasonic nozzle. With the mono-disperse droplet generator the long drying chamber ensures a residence time of a number of seconds, but this also allows droplet coalescence at fall heights >40?cm.     

Lactose Composite Carriers for Respiratory Delivery

Purpose  Lactose dry powder inhaler (DPI) carriers, constructed of smaller sub units (composite carriers), were evaluated to assess their potential for minimising drug–carrier adhesion, variability in drug–carrier forces and influence on drug aerosol performance from carrier–drug blends. Methods  Lactose carrier particles were prepared by fusing sub units of lactose (either 2, 6 or 10 μm) in saturated lactose slurry. The resultant composite particles, as well as supplied lactose, were sieve fractioned to obtain a 63–90 μm carriers. The carriers were evaluated in terms of size (laser diffraction) morphology (electron microscopy and atomic force microscopy), crystallinity and drug adhesion (colloid probe microscopy). In addition, blends containing drug and carrier were prepared and evaluated in terms of drug aerosol performance. Results  The surface morphology and physico-chemical properties of the composite carriers were significantly different. Depending on the initial primary lactose size, the composite particles could be prepared with different surface roughness. Variation in composite roughness could be related to the change in drug adhesion (via modification in contact geometry) and thus drug aerosol performance from drug–lactose blends. Conclusion  Composite based carriers are a potential route to control drug–carrier adhesion forces and variability thus allowing more precise control of formulation performance.     

Single-use disposable dry powder inhalers for pulmonary drug delivery

Importance of the field: The understanding of pulmonary drug delivery and thus its utilization for medical purposes has remarkably advanced over the last decades. It has been recognized that this route of administration offers many advantages and several drug delivery systems have been developed accordingly. Thereby, single-use disposable dry powder inhalers may be considered an economically and therapeutically valuable option for both local and systemic administration of drugs to treat a variety of different disease states.

Areas covered in this review/What the reader will gain: This review highlights the required characteristics and potential applications of single-use disposable dry powder inhalers considering advantages as well as limitations of these drug delivery devices. Until now, such drug delivery systems have not become widely accepted. Several devices are available or under development and a few products have reached or completed the clinical phase, but none of them have received market authorization as yet.

Take home message: Recent advances in formulation and device design, however, can be considered encouraging and should eventually lead to a wider establishment of single-use disposable dry powder inhalers in pulmonary drug delivery.