中国药典2010年版药用辅料标准浅析

《中华人民共和国药品管理法》第一百零二条规定：辅料,是指生产药品和调配处方时所用的赋形剂和附加剂。药用辅料虽然不是起治疗功效的活性物质,但它赋予药物一定剂型,而且与提高药物的疗效、降低不良反应有很大的关系,其质量可靠性和多样性是保证剂型和制剂先进性的基础。     

气雾剂，你喷对了吗

气雾剂,是将药物与适当的液化气体（也称为抛射剂）装于特定的装置中,使用时,借这种液化气体产生的压力使药物呈雾状喷出的一种剂型。常见的如哮喘病人使用的一些经口吸入的药物,但气雾剂不止这类．它还有外用剂型。你会用气雾剂吗？     

药用气雾剂的喷雾研究与环境保护

气雾剂是指将药物与适宜的抛射剂共同装封于具有特制阀门系统的耐压容器中所制成的一种给药系统,使用时借助抛射剂的压力,将容器中的内容物喷射成雾滴或泡沫等形式于呼吸道、阴道、鼻腔黏股或皮肤表面,发挥局部或全身作用,还可用于环境空间消毒。 气雾齐可分为吸入气雾剂、外用气雾剂和空间消毒气雾剂三类。气雾剂的应用范围越来越广,产品已从原来的哮喘治疗用气雾剂增加到抗生素药物、心血管药物、抗病毒药物、镇痛药、镇静药、外用的消炎镇痛药、激素类药物及抗过敏药物气雾剂等。近年来,国内又开发了多种中成药气雾剂,特别是以挥发油为有效成分的气雾剂,如艾叶油气雾剂、牡荆油气雾剂和芸香油气雾剂。此外,对于气雾剂或粉末吸入装置用于肽类及蛋白质类药物的吸人或鼻腔给药,从而替代注射给药途径     

漫谈气雾剂与喷雾剂

气雾剂、喷雾剂都是借助压力将药物喷出直接到达作用部位或吸收部位,具有准确定位、快速起效的特点,广泛应用于烫伤、气喘、耳鼻喉等,并在外形上很相似,故人们常将它们混为一谈,实际上它们是两种不同剂型,其主要区别在于它们的压力来源不同,气雾剂(英文名:Aerosol)是借抛射剂的压力将药物喷出,而喷雾剂是借助于机械(喷雾器或雾化器)作用。气雾剂中的抛射剂有高度挥发性,因而具有致冷效应,多次使用于受伤皮肤上可引起不适与刺激,而喷雾剂不含抛射剂,可弥补气雾剂的不足,但存在剂量不易控制、使用不便等缺点,为扬长避短,视具体药物选择适宜的剂型,如市场上的喘康速、喘乐定为气雾剂,大佛水、宁源为喷雾剂。     

药用咀嚼胶处方及其药用辅料组成的综述

现综述了国外有关药用咀嚼胶处方及药用辅料的组成,包括适合的药物、胶基、软化剂、甜味剂、矫味剂、着色剂等,以期为开发新产品提供剂型选择和处方研究参考.     

药用抛射剂含氯氟烃代用品的研究进展

气雾剂作为众多药物剂型中的一个分支,具有分布均匀、奏效快、使用方便、剂量小等特点,经过多年来的发展,现已广泛为人们所接受。传统的气雾制品采用含氯氟烃(chlorofluorocarbon,CFC)作为抛射剂。但由于CFC对大气臭氧层的破坏作用,近年来其应用受到了限制,国内外都在积极寻找CFC代用品,相继出现了无氯氟代烷烃如四氟乙烷,七氟丙烷等。由此也促使不含CFC的新型肺部药物传递系统取得了重大发展。本文对药用气雾剂中抛射剂CFC代用品的相关研究进展作一综述。     

加强对药用辅料的监管工作十分重要

药用辅料是药品的一个重要组份.其质量优劣直接影响到药品的质量及使用.药用辅料也一直是制约药物制剂发展的一个重要因素.随着药物新剂型的不断开发和应用,药用辅料的研发、生产、管理等工作越来越受到重视.     

制剂企业药用辅料内控质量标准的研究

药用辅料是药物制剂的重要组成成分,药用辅料质量与成品质量息息相关,本文结合国内外药典收载情况及作者自己工作经验,浅谈药用辅料内控质量标准的制定,为药品制剂企业药用辅料内控质量标准的建立提供参考。     

药用定量吸入气雾剂中氟里昂抛射剂替代的研究进展

氯氟烷烃（CFC）即氟里昂,因对臭氧层的破坏和温室效应而导致禁用,以其为抛射剂的药用吸入气雾剂将于2010年全面退出中国市场.国外对CFC替代的研究已有20年,并有一系列品种上市,而国内在该方面的研究几乎为空白.本文综述TCFC的替代概况、替代抛射剂氢氟烷烃的理化性质、气雾剂处方的影响因素、制剂的疗效和安全性等.     

关联审评制度下药用辅料质量标准浅析

目的：研究关联审评制度下药用辅料质量标准现状，帮助理解关联审评制度下药用辅料质量标准内涵和各质量标准间存在的关系。方法：详细介绍关联审评制度下药用辅料质量标准的分类及特点，着重对现行药用辅料备案管理制度和药用辅料备案标准的制定要求、状态、变更、效力和现状等进行系统归纳、阐述，同时也对药用辅料备案标准和药典标准间的关系进行了分析、探讨。结果与结论：药品辅料的质量标准是药用辅料质量的重要衡量尺度，包括药典标准、注册标准、备案标准和内控标准等，其中药用辅料药典标准是对该辅料质量控制的基本标准和门槛；关联审评新制度下产生的药用辅料备案标准是监管机构确认辅料质量的重要文件。在关联审评制度的新时期，在进一步加深对药用辅料各质量标准的内涵和关系理解的同时，一方面需要企业对其备案的药用辅料进行更加广泛、深入的研究，以便给审评人员在关联审评时提供更多的参考依据；另一方面需要监管机构持续完善我国药用辅料药典标准体系，促进国内药用辅料质量标准整体提升，有助于提高我国制剂整体质量、推进制剂创新发展。     

The 15th International Society of Aerosols in Medicine Congress. Perth, Australia, 14-18 March 2005

This international meeting brought together approximately 250 delegates from the pharmaceutical industry, academia, hospitals and government agencies, to discuss the latest research and development on areas related to inhalation aerosols. Fundamental science and applied research encompassing both the biological and physicochemical aspects were presented. There was a wide range of topics covered, from immune modulation to pharmaceutical regulatory issues, including aerosol clearance; industry innovations; aerosols and in utero effects; technical advances in imaging; inhalation catastrophes; as well as recent advances and future directions in aerosol delivery systems. This biennial congress has provided an excellent forum for stimulating fruitful discussion of aerosols in medicine.     

The 15th International Society of Aerosols in Medicine Congress

This international meeting brought together ～ 250 delegates from the pharmaceutical industry, academia, hospitals and government agencies, to discuss the latest research and development on areas related to inhalation aerosols. Fundamental science and applied research encompassing both the biological and physicochemical aspects were presented. There was a wide range of topics covered, from immune modulation to pharmaceutical regulatory issues, including aerosol clearance; industry innovations; aerosols and in utero effects; technical advances in imaging; inhalation catastrophes; as well as recent advances and future directions in aerosol delivery systems. This biennial congress has provided an excellent forum for stimulating fruitful discussion of aerosols in medicine.     

Nebulizer possibilities and limitations.

The ban of chlorofluorocarbon (CFC) propellants in metered dose inhalers (MDIs) gives rise to many alternatives and innovations: 1. CFC substitution by non-CFC propellants in MDIs. 2. battery driven miniaturized mechanical and piezoelectric nebulizers 3. revitalization of hand driven pocket nebulizers 4. self actuated dry powder inhalers (DPI's). All devices can be used with or without spacers. The choice for solid or liquid particles, e.g. powder or droplet aerosols, will also depend on the drug properties and the availability on the market for aerosol use. The nebulizer device will be chosen according to the medical need (emergency or long term treatment), the technical alternatives available in different countries, the possibility of patient cooperation (children, severely ill patients), and last not least marketing strategies and costs. The bronchial circulation is an important distribution system for medicine deposited by aerosol routes in the lung.     

Propellant-driven aerosols for delivery of proteins in the respiratory tract.

Metered-dose propellant-driven aerosols of an antigenically reactive protein were produced by combining bovine gammaglobulin (BGG) with one of several surfactants soluble in Freon or dimethylether propellants. Small-particle protein aerosols were most effectively produced by lyophilizing surfactants and proteins prior to the addition of propellants. Up to 26% of the total aerosolized protein was of respirable size. Aerosol metering valves delivering small volumes were most effective in producing respirable-sized (< or = 4 micron median mass aerodynamic diameter) protein aerosols. Proteins were suspended in liquified propellants as both propellant-soluble molecules and visible sedimenting clusters which both contributed to making respirable-sized protein aerosol particles. Electron microscopy showed that respirable-sized protein particles were composed of variable-sized chain aggregates of spherical subunits. Proteins were antigenic after suspension in liquified propellant and release as aerosols, but antigenicity diminished with extended propellant exposure. Local immunity in the respiratory tract is a key factor in resistance to respiratory infections. Metered-dose propellant-driven aerosols offer a potentially attractive method for delivering small-particle aerosols of immunizing antigens or other therapeutic proteins to the respiratory tract.     

Aerosolized drug delivery: fractional deposition of inhaled particles.

Delivery of drugs by aerosol is increasingly used as a means of providing therapy to both the lungs and to the rest of the body through absorption into the pulmonary circulation. The techniques, definitions, and terminology for aerosol delivery are not standardized or necessarily understood by the increasing number of clinicians and clinical investigators involved in these studies. This paper attempts to establish some definitions and guidelines for defining and characterizing deposition of aerosols in the respiratory tract. Some of the parameters that affect deposition are discussed (e.g., particle size, breathing pattern, airway caliber). It is suggested that these parameters be controlled or measured when characterizing new aerosol delivery systems for clinical investigations. These recommendations were discussed and agreed upon during an expert meeting on definitions and standards related to aerosols in medicine at the 8th Congress of ISAM.     

Formulation of advancing products of pulmonary medicine absorption

The author introduces the various possibilities of the production of medical aerosols ensuring pulmonary absorption. He also mentions the method of selecting the auxiliary materials formulated with propellants, and describes the characteristics of norfluran Dymel 134 and apafluran HFC 227. In the experimental section, he handles the development of an anxiolitic byciclo-heptane-type aerosol, for which the aim was to develop a homogeneous liquid-phase aerosol. For this he used a Freon 12/114 mixture and Dymel 134 propellants in a solvent mixture of ethanol and ethanol-propylene glycol. The solubility of byciclo-heptane could be significantly improved with beta-cyclodextrine. The formation of enclosure complex can be proved by IR spectrum, and the complete dissolution was furthered by the OH groups of the auxiliary material.     

Development of budesonide nanocluster dry powder aerosols: processing

Aerosolized medicine is one of the fastest growing areas in the pharmaceutical industry. Dry powder aerosols of pharmaceutical compounds are particularly attractive for the prevention and treatment of respiratory diseases but are also emerging as a treatment option for systemic diseases. Engineering particles in dry powder formulations can overcome many of the limitations of traditional inhaled pharmaceuticals. Here, a wet milling process for producing agglomerated budesonide nanoparticles (i.e., "NanoClusters") was explored. Parameters such as milling time and drug concentration were investigated, and the aerosol performance of dried budesonide NanoClusters was characterized. The wet milling process was able to produce aerosol particles composed entirely of budesonide. High emitted fraction and a large fine particle fraction suggested that the NanoCluster budesonide formulation would offer highly efficient delivery of drug throughout the lung.     

Tetrafluoroethane (RFC 134A) Propellant-Driven Aerosols of Proteins

Purpose. Develop metered-dose propellant-driven aerosols of proteins using tetrafluoroethane (HFC 134A) as propellant. Methods. Proteins were lyophilized with the propellant-soluble surfactants Triton X-100, Triton X-405, Laureth-9, Brij-30, Nonidet-40, and diethylene glycol monoethylether and then charged with propellants. Results. Small particle aerosols of the experimental protein bovine gamma globulin were produced. The fraction of aerosolized respirable-sized protein particles (<4–5 m) increased after dispersion of particles in propellant with agitation by shaking. Scanning electron microscopy of respirable-sized protein aerosols demonstrated bead-like particles in grape-like clusters. Vigorous shaking of propellant-suspended particles for 2 minutes or more reduced the size of clusters and reduced the diameters of the protein-containing subparticles that constituted the clusters. A 50:50 ratio of HFC 134A and dimethylether (DME) propellants improved the respirability of protein aerosols compared to HFC 134A as the sole propellant. Protein/surfactant particles first dispersed in DME and then diluted in HFC 134A propellant most efficiently produced respirable-sized, propellant-driven, protein aerosols. Conclusions. Metered-dose aerosols of respirable-sized proteins can be generated using HFC 134A and HFC 134A:DME blended propellants as an alternative to nebulized aqueous aerosols for delivering peptide-based pharmaceuticals to the respiratory tract.     

慢性气道疾病患者吸入气雾剂使用调查及药学监护

目的:了解患者使用吸入气雾剂的情况,提高药师药学监护水平。方法:调查呼吸内科住院部132例慢性气道疾病患者使用吸入气雾剂的基本情况、既往用药信息和使用吸入气雾剂的操作等,并对数据进行统计和对比分析。结果:所有初次使用吸入气雾剂的93例患者中,23例完全掌握吸入方法(24.73%),36例有1～2项操作错误(38.71%),34例患者有3或3项以上操作错误(36.56%)。93例患者中,低、高学历组吸入方法总掌握率分别为40.00%、81.13%(P<0.01),既往使用过吸入气雾剂的39例患者,曾接受过指导和未经过指导者吸入方法的总掌握率分别为100.00%、44.44%(P<0.01)。所有初次使用压力定量气雾吸入器和干粉吸入器的患者方法掌握率分别为60.71%、67.57%(P>0.05)。结论:经过药师的用药指导,患者能够更加熟练地掌握吸入气雾剂使用方法,药学监护对患者合理用药有重要意义。     

The Effect of Film Thickness on Thermal Aerosol Generation

Purpose Rapid heating of thin films of pharmaceutical compounds can vaporize the molecules, which leads to formation of aerosol particles of optimal size for pulmonary drug delivery. The aim of this work was to assess the effect of coated film thickness on the purity of a thermally generated (condensation) drug aerosol. Materials and Methods Pharmaceuticals in their free base form were spray-coated onto stainless steel foils and subsequently heated and vaporized in airflow via a rapid resistive heating of the foil. Aerosol particles were collected on filters, extracted, and analyzed using reverse phase HPLC to assess the amount of degradation induced during the vaporization process. Results Condensation aerosols of five pharmaceuticals were formed from a wide range of film coating thicknesses. All five showed a roughly linear trend of increasing aerosol purity with decreasing film thickness, although with quite different slopes. These findings are consistent with a model based on general vaporization and degradation kinetics. Small non-uniformities in the film do not significantly alter aerosol purity. Conclusions Rapid vaporization of pharmaceuticals coated as thin films on substrates is an efficient way of generating drug aerosols. By controlling the film thickness, the amount of aerosol decomposition can be minimized to produce high purity aerosols.