药典注射剂通则

附录ⅠB 注射剂注射剂系指药物与适宜的溶剂或分散介质制成的供注入体内的溶液，乳状液或混悬液及供注入体内的溶液、乳状液或混悬液及供临用前配制或稀释成溶液或混悬液的粉末或浓溶液的无菌制剂。

注射剂可分为注射液、注射用无菌粉末与注射用浓溶液。

注射液包括溶液型、乳状液型或混悬型注射液，可用于肌内注射、静脉注射、静脉滴注等。

其中，供静脉注射用的大体积（除另有规定外，一般不小于100ml）注射液也称静脉输液。

注射用无菌粉末系指药物制成的供临用前用适宜的无菌溶液配制成澄清溶液或均匀混悬液的无菌粉末或无菌块状物。

可用适宜的注射用溶剂配制后注射，也可用静脉输液配制后静脉滴注。

无菌粉末用溶剂结晶法、喷雾干燥法或冷冻干燥法等制得。

注射用浓溶液系指药物制成的供临用前稀释后静脉滴注用的无菌浓溶液。

注射液在生产与贮藏期间应符合下列有关规定。

一、溶液型注射液应澄明；除另有规定外，混悬型注射液中药物粒度应控制在15µm以下，含15～20µm （间有个别20～50µm）者，不得超过10%，若有可见沉淀，振摇时应容易分散均匀，混悬型注射液不得用于静脉注射或椎管注射；乳状液型注射液应稳定，不得有相分离现象，不得用于椎管注射。

静脉用乳状液型注射液中乳滴的粒度90%应在1µm以下，不得有大于5µm的乳滴。

除另有规定外，静脉输液应尽可能与血液等渗。

二、注射剂所用的原辅料应从来源及工艺等生产环节进行严格控制并应符合注射用的质量要求。

注射剂所用溶剂必须安全无害，并不得影响疗效额质量。

一般分为水性溶剂和非水性溶剂。

（1）水性溶剂最常用的为注射用水，也可用0.9%氯化钠溶液或其他适宜的水溶液。

（2）非水性溶剂常用的为植物油，主要为供注射用大豆油，其他还有乙醇、丙二醇和聚乙二醇等溶剂。

供注射用的非水性溶剂，应严格限制其用量，并应在品种项下进行相应的检查。

三、配制注射剂时，可根据药物的性质加入适宜的附加剂。

《我国药典》通则9201使用的药品类型一、引言我国药典是我国国家药典委员会颁布的一部权威的中药和中药材标准集合。

它对于我国的药品行业具有重要的指导作用，涵盖了丰富的药品和药材信息。

《我国药典》的通则9201主要规定了药品的使用类型，包括了常见的药品类型和用法用量等内容。

二、药品类型1.西药西药是指以化学合成方法或生物技术制备的药品，按照其药理作用和化学结构可分为多个类别，例如抗生素、抗病毒药、消炎药等。

在《我国药典》中，对于西药的使用类型主要包括了口服药、注射剂和外用药等。

其中，口服药适合于溶解度好、生物利用度高且不会被胃酸破坏的药物，而外用药适合于表皮疾病的治疗，注射剂适合于需要快速治疗的急危重症患者。

2.中药中药是指在我国传统医学理论指导下，采用天然药材为原料制剂的药品。

按照中药的性味归经可分为寒热药、温凉药、苦甘药等，而根据用法用量分类可分为口服剂、外用剂、注射剂等。

中药的使用类型在《我国药典》中有着详细的规定，强调了中药对于疾病的治疗特点和注意事项。

3.生物制品生物制品是指通过生物技术手段获得的治疗性制剂，例如血液制品、疫苗、生物制剂等。

根据其来源和用途可分为人血及其制品、动物源药品、细菌和真菌制品等。

生物制品的使用类型在《我国药典》中有着严格的规定和标准，旨在确保生物制品的安全性和有效性。

4.药物辅料药物辅料是指制药过程中所使用的辅助剂，例如赋形剂、增稠剂、溶剂等。

根据其用途和性质可分为固体辅料、液体辅料、气体辅料等。

《我国药典》对药物辅料的使用类型进行了规范和标准，以保证药品的制造过程和质量。

5.其他药品除了上述提到的药品类型，还有一些特殊的药品类型也被纳入了《我国药典》的规范范畴中，例如中草药提取物、中药配方颗粒、中药饮片等。

这些药品类型在药品的生产、质量控制和临床应用方面都有着特殊的要求，需要根据《我国药典》的规定进行操作。

三、结语《我国药典》通则9201使用的药品类型规范了药品的类别和使用要求，为我国的药品行业提供了重要的指导和标准。

药典中注射剂对抗氧剂的要求
中国药典2015年版四部 0102 注射剂通则中：配制注射剂时，可根据需要加入适宜的附加剂，如渗透压调节剂、pH 值调节剂、增溶剂、助溶剂、抗氧剂、抑菌剂、乳化剂、助悬剂等。

所用附加剂应不影响药物疗效，避免对检验产生干扰，使用浓度不得引起毒性或明显的刺激性。

常用的抗氧剂有亚硫酸钠、亚硫酸氢钠和焦亚硫酸钠等，一般浓度为0.1% 〜0.2%。

但一些产品由于其结构的特殊性，其主要成份在空气中极易氧化，有可能其抗氧剂用量需要超过0.2%时，主药才能比较稳定。

但有人说，如果抗氧剂用量比如亚硫酸氢钠用量大后，其过多的氢离子可能增加药液对血管的刺激性。

我们有一注射剂产品因主药成份极易氧化，虽然进行充氮处理并控制其残氧量，但稳定性并不是很好，通过对抗氧剂亚硫酸氢钠等用量的筛选，确定浓度为0.3%比较合适，同时进行了过敏性、溶血性、血管刺激性等试验，结果表明：家兔每日耳缘缓慢静脉滴注浓度为2.0mg/ml的该产品8ml/kg，另侧给予等体积的生理盐水，连续3次，于末次给药后24h取家兔耳缘静脉观察未见明显刺激反应。

表明该药血管刺激性试验符合要求。

EUROPEAN PHARMACOPOEIA 6.0ParenteralpreparationsMucoadhesive preparations DEFINITION Mucoadhesive preparations contain one or more active substances intended for systemic absorption through the buccal mucosa over a prolongedperiodof time.They may be supplied as mucoadhesive buccal tablets or as other mucoadhesive solid or semi-solid preparations.Mucoadhesive buccal tablets are prepared by compressionof mono-or multi-layeredtablets.They usually containhydrophilic polymers,which on wetting with the salivaproduce a flexible hydrogel that adheres to the buccal mucosa.PRODUCTION In the manufacture of mucoadhesive buccal tablets,measures are taken to ensure that they possess suitablemechanical strength to resist handling without crumbling or breaking.This may bedemonstratedby examining the Friability of uncoated tablets (2.9.7)and the Resistance to crushing of tablets (2.9.8).TESTS Dissolution .Unlessotherwisejustified and authorised,a suitable test is carried out to demonstrate the appropriate release of the active substance(s).01/2008:0520PARENTERAL PREPARATIONS Parenteralia The requirementsof this monograph do not necessarily apply to products derived fromhuman blood,toimmunological preparations,or radiopharmaceutical preparations.Special requirements may apply to preparations for veterinary use depending on the species of animal for which the preparation is intended.DEFINITION Parenteral preparations are sterilepreparations intended for administration by injection,infusion or implantation into the human or animal body.Parenteral preparations may require the use of excipients,for example to make the preparation isotonic with respect to blood,to adjustthe pH,to increase solubility,to prevent deterioration of the activesubstancesor to provideadequateantimicrobial properties,but not to adversely affect the intended medicinal action of the preparation or,at the concentrations used,to cause toxicity or undue local irritation.Containers for parenteral preparations are made as far as possible frommaterialsthat are sufficiently transparentto permit the visual inspection of the contents,except for implants and in other justified and authorised cases.Where applicable,the containers for parenteral preparations comply with the requirements for Materials used for the manufacture of containers (3.1and subsections)and Containers (3.2and subsections).Parenteral preparations are supplied in glass containers (3.2.1)or in other containers such as plastic containers (3.2.2,3.2.2.1and 3.2.9)and prefilled syringes.The tightness of the containeris ensured bysuitablemeans.Closuresensure a good seal,prevent the access of micro-organisms and other contaminants and usually permit the withdrawal ofa part or the whole of the contents without removal of the closure.The plasticmaterials or elastomers (3.2.9)used to manufacture the closures are sufficiently firm and elastic to allow the passage of a needle with the least possible shedding ofparticles.Closures for multidose containers aresufficiently elastic to ensure that the puncture is resealedwhen the needle is withdrawn.Severalcategories of parenteral preparations may be distinguished:—injections,—infusions,—concentrates for injections or infusions,—powders for injections or infusions,—gels for injections,—implants.PRODUCTIONDuringthe developmentof a parenteral preparation,theformulation for which contains an antimicrobial preservative,the effectiveness of the chosen preservative shall be demonstratedto the satisfaction of the competent authority.A suitable test method togetherwithcriteria forjudgingthe preservative properties of the formulation are provided under Efficacy of antimicrobial preservation (5.1.3).Parenteral preparations are prepared using materials and methods designed to ensure sterility and to avoidthe introduction of contaminants and thegrowth ofmicro-organisms.Recommendations on this aspect areprovided in the text on Methods of preparation of sterile products (5.1.1).Water used in the manufacture of parenteral preparationscomplies with the requirements of water for injections in bulk stated in the monograph on Water for injections (0169).TESTSParticulate contamination:sub-visible particles (2.9.19).For preparations for human use,solutions for infusion orsolutions for injection comply with the test.Inthe case of preparations for subcutaneous or intramuscular injection,higher limits may be appropriate.Radiopharmaceutical preparations are exempt from these requirements.Preparations for which the label states thatthe product is to be used with a final filter are exempt from these requirements,providing it has been demonstrated that the filter delivers a solution that complies with the test.For preparations for veterinary use,whensupplied in containers with a nominal content of more than 100ml and when the content is equivalent to a dose of more than1.4ml per kilogram of body mass,solutions for infusion orsolutions for injection comply with the test for particulate contamination:sub-visible particles.Sterility (2.6.1).Parenteral preparations comply with the test for sterility.STORAGEIn a sterile,airtight,tamper-proof container.LABELLINGThe label states:—the name andconcentration of any added antimicrobial preservative,—where applicable,that the solution is to be used in conjunction with a final filter,—where applicable,that the preparation is free frombacterial endotoxins or that it is apyrogenic.General Notices (1)apply to all monographs and other texts 735Parenteral preparations EUROPEAN PHARMACOPOEIA6.0InjectionsDEFINITIONInjections are sterile solutions,emulsions or suspensions. They are prepared by dissolving,emulsifying or suspending the active substance(s)and any added excipients in water,in a suitable non-aqueous liquid,that may be non-sterile where justified,or in a mixture of these vehicles.Solutions for injection,examined under suitable conditions of visibility,are clear and practically free from particles. Emulsions for injection do not show any evidence of phase separation.Suspensions for injection may show a sediment which is readily dispersed on shaking to give a suspension which remains sufficiently stable to enable the correct dose to be withdrawn.Multidose preparations.Multidose aqueous injections contain a suitable antimicrobial preservative at an appropriate concentration except when the preparation itself has adequate antimicrobial properties.When a preparation for parenteral use is presented in a multidose container, the precautions to be taken for its administration and more particularly for its storage between successive withdrawals are given.Antimicrobial preservatives.Aqueous preparations which are prepared using aseptic precautions and which cannot be terminally sterilised may contain a suitable antimicrobial preservative in an appropriate concentration.No antimicrobial preservative is added when:—the volume to be injected in a single dose exceeds15ml, unless otherwise justified,—the preparation is intended for administration by routes where,for medical reasons,an antimicrobial preservative is not acceptable,such as intracisternally,epidurally,intrathecally or by any route giving access to thecerebrospinal fluid,or intra-or retro-ocularly.Such preparations are presented in single-dose containers.PRODUCTIONIn the manufacture of injections containing dispersed particles,measures are taken to ensure a suitable and controlled particle size with regard to the intended use. Single-dose preparations.The volume of the injection in a single-dose container is sufficient to permit the withdrawal and administration of the nominal dose using a normal technique(2.9.17).TESTSUniformity of dosage units.Single-dose suspensions for injection comply with the test for uniformity of dosage units (2.9.40)or,where justified and authorised,with the test for uniformity of content shown below.Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.Uniformity of content(2.9.6).Unless otherwise prescribed or justified and authorised,single-dose suspensions for injection with a content of active substance less than2mg or less than2per cent of the total mass comply with test A for uniformity of content of single-dose preparations.Ifthe preparation contains more than one active substance, the requirement applies only to those substances that correspond to the above conditions.Bacterial endotoxins-pyrogens.A test for bacterial endotoxins(2.6.14)is carried out or,where justified and authorised,the test for pyrogens(2.6.8).Recommendations on the limits for bacterial endotoxins are given in chapter2.6.14.Preparations for human use.The preparation complies with a test for bacterial endotoxins(2.6.14)or with the test for pyrogens(2.6.8).Preparations for veterinary use.When the volume to be injected in a single dose is15ml or more and is equivalent to a dose of0.2ml or more per kilogram of body mass,the preparation complies with a test for bacterial endotoxins (2.6.14)or with the test for pyrogens(2.6.8).Any preparation.Where the label states that the preparation is free from bacterial endotoxins or apyrogenic,respectively, the preparation complies with a test for bacterial endotoxins (2.6.14)or with the test for pyrogens(2.6.8),respectively.InfusionsDEFINITIONInfusions are sterile,aqueous solutions or emulsions with water as the continuous phase.They are usually made isotonic with respect to blood.They are principally intended for administration in large volume.Infusions do not contain any added antimicrobial preservative.Solutions for infusion,examined under suitable conditions of visibility are clear and practically free from particles. Emulsions for infusion do not show any evidence of phase separation.PRODUCTIONIn the manufacture of infusions containing dispersed particles,measures are taken to ensure a suitable and controlled particle size with regard to the intended use. The volume of the infusion in the container is sufficientto permit the withdrawal and administration of the nominal dose using a normal technique(2.9.17).TESTSBacterial endotoxins-pyrogens.They comply with a test for bacterial endotoxins(2.6.14)or,where justified and authorised,with the test for pyrogens(2.6.8).For the latter test inject10ml per kilogram of body mass into each rabbit, unless otherwise justified and authorised. Concentrates for injections or infusions DEFINITIONConcentrates for injections or infusions are sterile solutions intended for injection or infusion after dilution.They are diluted to a prescribed volume with a prescribed liquid before administration.After dilution,they comply with the requirements for injections or for infusions.TESTSBacterial endotoxins-pyrogens.They comply with the requirements prescribed for injections or for infusions,after dilution to a suitable volume.Powders for injections or infusions DEFINITIONPowders for injections or infusions are solid,sterile substances distributed in their final containers and which,when shaken with the prescribed volume of a prescribed sterile liquid rapidly form either clear and736See the information section on general monographs(cover pages)EUROPEAN PHARMACOPOEIA 6.0Patches,transdermal practically particle-free solutions or uniform suspensions.After dissolution or suspension,they comply with therequirements for injections or for infusions.Freeze-dried products for parenteral use are considered aspowders for injections or infusions.PRODUCTION The uniformity of contentand uniformityof mass offreeze-dried products for parenteral use are ensured by the in-process control of the amount of the solution prior to freeze-drying.TESTS Uniformity of dosage units .Powders for injections or infusions comply with the test for uniformity of dosage units (2.9.40)or,where justified and authorised,with the tests for uniformity of content and/or uniformity of mass shown below.Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.Uniformity of content (2.9.6).Unless otherwise prescribed or justifiedand authorised,powders for injections or infusions with a content of active substance less than 2mgor less than 2per cent of the total mass,or with a unit mass equal to or less than 40mg comply with test A for uniformity of content of single-dose preparations.If the preparation contains more than one active substance,the requirement applies only to those substances that correspond to the above conditions.Uniformity of mass (2.9.5).Powders for injections or infusions complywith the test for uniformity of mass ofsingle-dose preparations.If the test for uniformity of content is prescribed for all the active substances,the test for uniformity of mass is not required.Bacterial endotoxins-pyrogens.Theycomplywith the requirements prescribed for injections or for infusions,after dissolution or suspension in a suitable volume of BELLING The label states the instructions for the preparation of injections and infusions.Gels for injections DEFINITION Gels for injections are sterile gels with a viscosity suitable to guarantee a modified release of the active substance(s)at the site of injection.Implants DEFINITION Implants are sterile,solid preparations of a size and shape suitable for parenteral implantation and release of the active substance(s)over an extended period of time.Each dose is provided in a sterile container.01/2008:1011PATCHES,TRANSDERMALEmplastra transcutaneaDEFINITIONTransdermal patches are flexible pharmaceutical preparations of varying sizes,containing one or more activesubstances.Theyare intendedto be applied to the unbrokenskin in order to deliver the active substance(s)to the systemiccirculation after passing through the skin barrier.Transdermalpatches normally consist of an outer covering which supports a preparation which contains the activesubstance(s).The transdermal patches are covered on thesite of the release surface of the preparation by a protective liner,which is removed before applying the patch to the skin.The outer covering is a backing sheet impermeable to the active substance(s)and normally impermeable to water,designed to support and protect the preparation.The outer covering may have the same dimensions as the preparation or it may be larger.In the latter case the overlapping border of the outer covering is covered by pressure-sensitive adhesive substances which assure the adhesion of the patchto the skin.The preparation contains the active substance(s)togetherwith excipients such as stabilisers,solubilisers or substances intended to modify the release rate or to enhance transdermal absorption.It may be a single layer or multi-layer solid orsemi-solid matrix,and in this case it is the compositionand structure of the matrix which determines the diffusion pattern of the active substance(s)to the skin.The matrix may contain pressure-sensitive adhesives which assure theadhesion of the preparation to the skin.The preparation may exist as a semi-solid reservoir one side of which is amembranewhich may control the release and the diffusion of the active substance(s)from the preparation.The pressure-sensitive adhesive substances may,in this case,beapplied to some or all parts of the membrane,or only aroundthe border of the membrane of the outer covering.When applied to the dried,clean and unbrokenskin,thetransdermalpatch adheres firmly to the skin by gentle pressure of the hand or the fingers and can be peeled offwithout causing appreciable injury to the skin or detachment of thepreparation from the outer covering.The patch mustnot be irritant or sensitising to the skin,even after repeated applications.The protective liner generally consists of a sheet of plastic ormetal material.When removed,the protective liner does notdetach the preparation (matrix or reservoir)or the adhesive from the patch.Transdermal patches are normally individually enclosed in sealed sachets.PRODUCTIONInthe manufacture,packaging,storage and distributionof transdermalpatches suitable means are taken to ensuretheir microbial quality;recommendations onthis aspect are provided in the text on Microbiological quality ofpharmaceutical preparations (5.1.4).TESTSUniformity ofdosageunits .Transdermal patchescomplywith the test for uniformity of dosage units (2.9.40)or,where justified and authorised,with the test for uniformity General Notices (1)apply to all monographs and other texts 737。