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。     

吸入粉雾剂的研究进展

综述了提高吸入粉雾剂雾化性能的方法、粉雾剂的体外评价手段和生物药剂学研究方法等方面的进展状况.着重介绍了大多孔粒子和纳米粒的聚合物对提高粉雾剂物化性能的作用.     

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。     

乳糖载体表面形态对吸入粉雾剂处方混合及分散性能的影响

乳糖的表面形态会对混合过程和吸入粉雾剂(DPI)处方的分散性能产生影响.本研究通过将乳糖(InhaLac230?)在高湿环境中放置72 h,得到了与未处理乳糖粒径相似、晶型相同,但表面较光滑的另一种载体颗粒.将2种乳糖颗粒与微粉化马来酸氯苯那敏分别进行混合,得到DPI粉末研究模型.测定了混合过程中不同混合时间点的粉末静...     

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。     

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。     

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。     

吸入粉雾剂的处方研究和制备工艺

吸入粉雾剂在治疗肺部疾病,如哮喘、慢性阻塞性肺病中应用广泛.文中广泛查阅欧盟、美国等国的吸入粉雾剂研发的要求,结合国内该剂型的研发和审批情况,对吸入粉雾剂的组成、处方筛选以及制备工艺进行详细的阐述.对吸入粉雾剂在处方筛选与制备过程中的影响因素加以详细讨论,为研发粉雾剂药学工作者提供有益的参考.     

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...     

辛伐他汀吸入粉雾剂的制备与质量评价

目的制备辛伐他汀吸入粉雾剂,并进行质量评价。方法采用冷冻干燥法制备辛伐他汀微粉,将微粉与乳糖载体混合制备吸入粉雾剂,并通过正交实验优化处方,测定其粒径、密度、含水量、排空率和有效沉积率。结果辛伐他汀微粉与乳糖Inhalac~70按照1∶1比例混匀制成的吸入粉雾剂,平均粒径在10μm以下,堆密度和振实密度分别为0.192±0.012和0.285±0.013g·mL~(-1),含水量为2.36%±0.22%,排空率为97.8%,有效沉积率为32.7%。结论按照选定的处方和制备方法制得的吸入粉雾剂流动性好、排空率合格、有效部位药物沉积量高,符合吸入粉雾剂要求。     

The Influence of Fine Excipient Particles on the Performance of Carrier-Based Dry Powder Inhalation Formulations

The inclusion of a small amount of fine particle excipient in a carrier-based dry powder inhalation system is a well researched technique to improve formulation performance and is employed in the pharmaceutical industry. The removal of intrinsic fines from a lactose carrier has been found to decrease formulation performance, whereas adding fines of many different materials into formulations increased performance. Changing the particle size of these fines, the amount added and the technique by which they were prepared also affected formulation behaviour. Despite this body of research, there is disagreement as to the mechanism by which fines improved formulation performance, with two main hypotheses presented in the literature. The first hypothesis suggested that fines prevent the drug from adhering to the strongest binding sites on the carrier, whilst the second proposed that fine particles of drug and excipient form mixed agglomerates that are more easily dispersed and deaggregated during aerosolisation. The evidence in support of each hypothesis is limited and it is clear that future research should aim to produce stronger mechanistic evidence. The investigation of interparticulate interactions using techniques such as atomic force microscopy and inverse gas chromatography may prove useful in achieving this aim.     

乳糖在干粉吸入剂中的应用

目的 综述了乳糖在干粉吸入剂(dry powder inhalers,DPI)中的应用,为DPI的研究和开发提供思路。方法 查阅国内外相关文献,综述了载体乳糖(coarse carrier)的不同性质及加入微粉化乳糖(fine particles)对DPI肺部沉积的影响。结果 DPI中的药物经微粉化后,其雾化性能下降。乳糖应用于DPI中的研究分析表明,乳糖可以有效改善DPI中药物的雾化性能,从而提高药物在肺部的沉积效率,发挥最佳药效。结论 加入不同性质的载体乳糖和微粉化乳糖可以有效改善药物在肺部的沉积效率。     

丙酸倍氯米松粉雾剂质量控制的研究

研究了丙酸倍氯米松胶囊型粉雾剂的质量控制,确定了微粒大小的测定方法,比较了手工和机械制备的载体的粉体性质,进行了体外模拟试验,测试了湿度及外包装对该制剂吸入效果的影响。     

低密度多孔性颗粒在干粉吸入剂中的应用

评述了低密度多孔性颗粒能从改善药物的给药剂量重现性、提高沉积性能和降低巨嗜细胞的吞噬作用等多方面提高干粉吸入剂的性能,并介绍了它的几种制备方法。     

干粉吸入剂空气动力学分散模型的建立和验证

在Weiler干粉粒子聚集体全分散理论模型基础上,以硫酸沙丁胺醇为模型药物,建立了一种更加深入的千粉吸入剂空气动力学分散模型.硫酸沙丁胺醇干粉吸入剂体外沉积试验表明,该模型可预测干粉粒子的空气动力学分散行为,并可结合计算流体动力学,估算干粉吸入剂在吸入装置中的分散及微细粒子分数.     

Protein Deposition from Dry Powder Inhalers: Fine Particle Multiplets as Performance Modifiers

Purpose. To evaluate the use of carrier-based dry powder aerosols for inhalation delivery of proteins and examine the effect of fine particle excipients as potential formulation performance modifiers. Methods. Bovine serum albumin (BSA) was co-processed with malto-dextrin by spray-drying to produce model protein particles. Aerosol formulations were prepared by tumble mixing protein powders with -lactose monohydrate (63–90 m) or modified lactoses containing between 2.5 and 10% w/w fine particle lactose (FPL) or micronised polyethylene glycol 6000. Powder blends were characterised in terms of particle size distribution, morphology and powder flow. Formulation performance in Diskhaler^® and Rotahaler^® devices was investigated using a twin stage impinger operating at 60 1 min^–1. Results. Inhalation performance of binary ordered mixes prepared using BSA-maltodextrin and lactose (63–90 m) was improved by addition of FPL and micronised PEG 6000. For the addition of 5% w/w FPL the protein fine particle fraction (0.5–6.4 m) using the Diskhaler^® was increased from 31.7 ± 2.4% to 47.4 ± 2.2%. Inclusion of FPL and micronised PEG 6000 changed the bulk properties of inhalation powders and reduced powder flow but did not affect device emptying. Unexpectedly, improvements in performance were found to be independent of the order of addition of FPL to the ternary powder formulations. SEM studies revealed that this was probably the result of a redistribution of protein particles between the coarse carrier lactose component and added FPL during mixing. Conclusions. Fine particle excipients can be used to improve the performance of carrier-based protein dry powder aerosols. Mechanistically, enhancement of performance is proposed to result from a redistribution of protein particles from coarse carrier particles to the fine particle component in the ternary mix.     

鲑降钙素经鼻干粉吸入剂的制备及评价

采用冷冻干燥法制备鲑降钙素生物黏附附聚物，研究表面活性剂泊洛沙姆用量对容器吸附降钙素的作用；用改进的Twin-impinger进行体外模拟试验，并测定家兔静脉和经鼻腔给药后的血钙降低情况。结果表明，当泊洛沙姆188浓度为0．25％时，具良好的抗容器吸附主药能力，与溶液型喷雾剂和胶囊干粉吹入剂相比，主动吸入的泡囊型干粉吸入剂较溶液型喷雾剂更易在具治疗意义的部位沉积；家兔试验表明，鼻腔给药后，其降血钙作用相当于静注给药的72％，达峰时间为3．5h（静注为1．5h），作用时间可持续约10h（静注约为7h）。     

Preparation and Quality Evaluation of Salvianolic Acids and Tanshinones Dry Powder Inhalation

Salvianolic acids and tanshinones both exhibit efficacy in treating idiopathic pulmonary fibrosis (IPF), but their formulation limits their clinical use. This study aimed to prepare the salvianolic acids and tanshinones dry powder for inhalation (SPI) to achieve pulmonary delivery for the treatment of IPF. The variable quantities of salvianolic acids and tanshinones composite powder were optimized using the central composite design-response surface method. Different carriers with various drug-carrier ratios were optimized to prepare SPI. The final optimized formulation of SPI was as follows: InhaLac 230^® was selected as the carrier with drug:carrier = 1:6, and the milled lactose InhaLac 400^® was added at 5%. The developed SPI characterized with an angle of repose 52.46 ± 1.04°, Carr's index of 34.00 ± 0.50% and showed high lung deposition in vitro, indicating the potential of pulmonary delivery for the treatment of IPF.     

Formulation and Characterization of Lipid-Coated Tobramycin Particles for Dry Powder Inhalation

Purpose This study was conducted to develop and evaluate the physicochemical and aerodynamic characteristics of lipid-coated dry powder formulations presenting particularly high lung deposition. Methods Lipid-coated particles were prepared by spray-drying suspensions with different concentrations of tobramycin and lipids. The solid-state properties of the formulations, including particle size and morphology, were assessed by scanning electron microscopy and laser diffraction. Aerosol performance was studied by dispersing the powders into a Multistage Liquid Impinger and determining drug deposition by high-performance liquid chromatography. Results Particle size distributions of the formulations were unimodal, narrow with more than 90% of the particles having a diameter of less than 2.8 μm. All powder formulations exhibited mass median diameters of less than 1.3 and 3.2 μm, as determined by two different laser diffraction methods, the Malvern's Mastersizer? and Spraytec?, respectively. The fine particle fraction varied within a range of 50.5 and 68.3%. Conclusions Lipid coating of tobramycin formulations resulted in a reduced agglomeration tendency and in high fine particle fraction values, thus improving drug deposition. The very low excipients content (about 5% m/m) of these formulations offers the benefit of delivering particularly huge concentrations of antibiotic directly to the site of infection, while minimizing systemic exposure, and may provide a valuable alternative treatment of cystic fibrosis.