欧洲药典注射剂通则
USP39 注射剂通则
tion as constituted for administration are not included in the individual monographs on sterile dry solids or liquid concentrates. However, in the interest of assuring the quality of injection preparations as they are actually administered, the following non-destructive tests are provided for demonstrating the suitability of constituted solutions when they are prepared just prior to use.Completeness and Clarity of Solution—Constitute the solution as directed in the labeling supplied by the manufacturer for the sterile dry dosage form.A:The solid dissolves completely, leaving no visible residue as undissolved matter.B:The constituted solution is not significantly less clear than an equal volume of the diluent or of Purified Water contained in a similar vessel and examined similarly.Particulate Matter—Constitute the solution as directed in the labeling supplied by the manufacturer for the sterile dry dos-age form: the solution is essentially free from particles of foreign matter that can be observed on visual inspection.á1ñ INJECTIONS AND IMPLANTED DRUG PRODUCTS(PARENTERALS)—PRODUCT QUALITY TESTS(Chapter to become official May 1, 2016)(Current chapter name is á1ñ Injections)INTRODUCTIONParenteral drug products include both injections and implanted drug products that are injected through the skin or other external boundary tissue, or implanted within the body to allow the direct administration of the active drug substance(s) into blood vessels, organs, tissues, or lesions. Injections may exist as either immediate- or extended-release dosage forms. Implan-ted parenteral drug products are long-acting dosage forms that provide continuous release of the active drug substance(s) of-ten for periods of months to years. For systemic delivery, they may be placed subcutaneously; for local delivery, they may be placed in a specific region of the body. Routes of administration for parenteral drug products include intravenous, intraventric-ular, intra-arterial, intra-articular, subcutaneous, intramuscular, intrathecal, intracisternal, and intraocular.Parenteral dosage forms include solutions, suspensions, emulsions, sterile powders for solutions and suspensions (including liposomes), implants (including microparticles), and products that consist of both a drug and a device such as drug-eluting stents. The reader is directed to Pharmaceutical Dosage Forms á1151ñ1 and to the later sections of this chapter for additional descriptions of dosage forms that fall into the general category of parenteral drug products. Nomenclature á1121ñ1 provides information on nomenclature used to establish USP names and monograph titles for parenteral drug products.Chapter á1ñ provides a framework to support the revision and the development of individual monographs, and is not meant to replace individual monographs. Chapter á1ñ provides lists of common product quality test requirements in a concise and a coherent fashion. The chapter is divided into four main sections: (1) universal product quality tests that are applicable to pa-rental dosage forms; (2) specific product quality tests, which are tests that should be considered in addition to Universal Tests;(3) product quality tests for specific dosage forms, which lists all the applicable tests (Universal and Specific) for the specific dosage form; and (4) product performance tests.If a monograph exists, it will reference á1ñ or indicated chapter parts. If a specific drug product monograph is missing (not in existence), the general chapters provide the quality tests that can be used by manufacturers until the dosage form monograph is developed by USP.The Pharmacopeial definitions for sterile preparations for parenteral use may not apply to some biologics because of their special nature and licensing requirements (see Biologics á1041ñ1). However, some biological finished drug products containing “Injection” in the monograph title must meet the requirements of á1ñ or indicated chapter subparts, where it is specified in the monograph.Drug Product Quality and Drug Product Performance TestsProcedures and acceptance criteria for testing parenteral drug products are divided into two categories: (1) those that assess product quality attributes, e.g., identification, sterility, and particulate matter, and are contained in this chapter and (2) those that assess product performance, e.g., in vitro release of the drug substance from the drug product. Whereas quality tests as-sess the integrity of the dosage form, the performance tests assess performance (bioavailability) after the product has been administered to the patient. A product performance test, i.e., drug release test for suspensions, emulsions, powder for suspen-sion (including microparticles and liposomes), and drug-eluting stents, should be carried out using appropriate test proce-dures.1All listed chapters above á1000ñare for information purposes only; they may be helpful but are not mandatory.Change to read:PRODUCT QUALITY TESTS COMMON TO PARENTERAL DOSAGE FORMSUniversal TestsUniversal tests are listed below and are applicable to parenteral dosage forms.Description: A qualitative description of the dosage form should be provided. The acceptance criteria should include the fi-nal acceptable appearance. If color changes during storage, a quantitative or a semiquantitative procedure may be appropri-ate. This section specifies the content or the label claim of the article (see Labeling á7ñ). Additional information about common-ly used terms and definitions can be found in Nomenclature á1121ñ1.Identification:Identification tests are discussed in General Notices and Requirements 5.40. Identification tests should establish the identity of the drug or drugs present in the article and should discriminate between compounds of closely related structure that are likely to be present. The most conclusive test for identity is the IR absorption spectrum (see Atomic Absorption Spec-troscopy á852ñ, Fluorescence Spectroscopy á853ñ, Mind-Infrared Spectroscopy á854ñ, Near-Infrared Spectroscopy á856ñ, Ultraviolet-Visible Spectroscopy á857ñ,(CN 1-May-2016) and Spectrophotometric Identification Tests á197ñ). If no suitable IR spectrum can be ob-tained, other analytical methods can be used. Near-infrared or Raman spectrophotometric methods also could be acceptable for the sole identification of the drug product formulation (see Near-Infrared Spectrophotometry á1119ñ1 and Raman Spectrosco-py á1120ñ1). Identification solely by a single chromatographic retention time is not regarded as specific. However, the use of two chromatographic procedures in which the separation is based either on different principles or a combination of tests in asingle procedure can be acceptable (see Chromatography á621ñ and Thin-Layer Chromatographic Identification Test á201ñ). Addi-tional information regarding identification tests can be found in Identification Tests—General á191ñ and Mass Spectrometryá736ñ.Assay: A specific and stability-indicating test should be used to determine the strength (content) of the drug product. In ca-ses where the use of a nonspecific assay is justified, other supporting analytical procedures should be used to achieve overallspecificity. A specific procedure should be used when there is evidence of excipient interference with the nonspecific assay.Impurities:Tests for Impurities are discussed in General Notices and Requirements 5.60. All articles should be tested to ensure that they meet the requirements.Foreign and particulate matter:Articles intended for parenteral administration should be prepared in a manner designed to exclude particulate matter as defined in Subvisible Particulate Matter in Therapeutic Protein Injections á787ñ, Particulate Matter in Injections á788ñ, and Particulate Matter in Ophthalmic Solutions á789ñ, as well as excluding other foreign matter as appropriate for the dosage form. Each final container of all parenteral preparations should be inspected to the extent possible for the pres-ence of observable foreign and particulate matter (hereafter termed visible particulates) in its contents. The inspection process should be designed and qualified to ensure that every lot of all parenteral preparations is essentially free from visible particu-lates, as defined in Visible Particulates in Injections á790ñ. Qualification of the inspection process should be performed with refer-ence to particulates in the visible range and those particulates that might emanate from the manufacturing or filling process.Every container in which the contents show evidence of visible particulates must be rejected. The inspection for visible particu-lates may take place during examination for other critical defects such as cracked or defective containers or seals or when char-acterizing the appearance of a lyophilized product.When the nature of the contents or the container–closure system permits only limited inspection of the total contents, the 100% inspection of a lot should be supplemented with the inspection of constituted (e.g., dried) or withdrawn (e.g., from a dark amber container) contents of a sample of containers from the lot.Large-volume injections for single-dose infusion, small-volume injections, and pharmacy bulk packages (PBP) are subject to the light obscuration or microscopic procedures and limits for subvisible particulate matter set forth in á788ñ, unless otherwise specified in the chapter or in the individual monograph. An article packaged as both a large-volume and a small-volume injec-tion meets the requirements set forth for small-volume injections where the container is labeled as containing 100 mL or less.It meets the requirements set forth for large-volume injections for single-dose infusion where the container is labeled as con-taining more than 100 mL.Sterility:The sterility of all drug products intended for parenteral administration should be confirmed by the use of methods described in Sterility Tests á71ñ or by an approved alternative method.Bacterial endotoxins:All articles intended for parenteral administration should be prepared in a manner designed to limit bacterial endotoxins as defined in Bacterial Endotoxins Test á85ñ or Pyrogen Test á151ñ.Container content:Container contents should be determined when appropriate (see the proposed general test chapterContainer Content for Injections á697ñ).Leachables and extractables:The packaging system should not interact physically or chemically with the preparation to al-ter its strength, quality, or purity beyond the official or established requirements. The packaging system should meet the re-quirements in Elastomeric Closures for Injections á381ñ, Packaging and Storage Requirements á659ñ, Containers—Glass á660ñ,Plastic Packaging Systems and their Materials of Construction á661ñ(CN 1-May-2016), Plastic Materials of Construction á661.1ñ, andPlastic Packaging Systems for Pharmaceutical Use á661.2ñ. Further information regarding packaging systems testing may be found in Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems á1663ñ and Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems á1664ñ.Container closure integrity:The packaging system should be closed or sealed in such a manner as to prevent contamina-tion or loss of contents. Validation of container integrity must demonstrate no penetration of microbial contamination or gain or loss of any chemical or physical parameter deemed necessary to protect the product (see Sterile Product Packaging—Integrity Evaluation á1207ñ).Labeling:All articles intended for parenteral administration should meet the labeling requirements defined in Labeling á7ñ).Specific TestsIn addition to the universal tests listed above, the following specific tests may be considered on a case-by-case basis and, when appropriate, are referenced in the USP–NF monograph.Physicochemical properties:These include such properties as Osmolality and Osmolarity á785ñ, pH á791ñ, Specific Gravityá841ñ, and Viscosity—Capillary Methods á911ñ.Uniformity of dosage units:This test is applicable for parenteral drug products and dosage forms packaged in single-unit containers. It includes both the mass of the dosage form and the content of the active substance in the dosage form (see Uniformity of Dosage Units á905ñ).Vehicles and added substances:There are other vehicles, both aqueous and nonaqueous, beyond those that are discussed below. All vehicles should be suitable for their intended use and not impact drug product quality.Aqueous vehicles—Aqueous vehicles must meet the requirements of Pyrogen Test á151ñ or Bacterial Endotoxins Test á85ñ, which-ever is specified in the monograph. Water for Injection is generally used as the vehicle. Sodium chloride or dextrose may be added to render the resulting solution isotonic, and Sodium Chloride Injection or Ringer's Injection may be used in whole or in part instead of Water for Injection.Nonaqueous vehicles—Fixed oils are classified under Nonaqueous vehicles. Fixed oils used as vehicles are of vegetable origin and are odorless. They meet the requirements in the test for Solid Paraffin in the Mineral Oil monograph with the cooling bath maintained at 10°.Also meet the requirements of the following tests:•Saponification Value (see Fats and Fixed Oils á401ñ): Between 185 and 200•Iodine Value (see á401ñ): Between 79 and 141•Unsaponifiable Matter (see á401ñ): NMT 1.5%•Acid Value (see á401ñ): NMT 0.2•Peroxide Value (see á401ñ): NMT 5.0•Water, Method Ic (from Water Determination á921ñ): NMT 0.1%•Limit of Copper, Iron, Lead, and Nickel: [N OTE—The test for nickel is not required if the oil has not been subjected to hydro-genation, or a nickel catalyst has not been used in processing.] Proceed as directed in Fats and Fixed Oils á401ñ, Trace Met-als or Elemental Impurities—Procedures á233ñ. Meet the requirements in Elemental Impurities—Limits á232ñ.Synthetic mono- or diglycerides of fatty acids may be used provided they are liquid and remain clear when cooled to 10° and have a Iodine Value of NMT 140.Added substances—Suitable substances may be added to preparations in order to increase stability or usefulness unless they are proscribed in the monograph. No coloring agent may be added to a preparation solely for the purpose of coloring the finished preparation (see General Notices and Requirements 5.20 and Antimicrobial Effectiveness Testing á51ñ).Observe special care in the choice and use of added substances in preparations with volumes that exceed 5 mL. The follow-ing limits prevail unless otherwise directed:•Mercury and cationic surface-active agents: NMT 0.01%•Chlorobutanol, cresol, phenol, and similar substances: NMT 0.5%•Sulfur dioxide or an equivalent amount of sulfite, bisulfite, or metabisulfite of potassium or sodium: NMT 0.2% Antimicrobial preservative:Antimicrobial agents must be added to preparations intended for injection that are packaged in multiple-dose containers unless one of the following conditions prevails: (1) there are different directions in the individual monograph; (2) the substance contains a radionuclide with a physical half-life of less than 24 h; or (3) the active ingredients are themselves antimicrobial. Substances must meet the requirements of Antimicrobial Effectiveness Testing á51ñ and Antimicrobi-al Agents—Content á341ñ.Water content:The water content of freeze-dried (lyophilized) products should be determined when appropriate (see Water Determination á921ñ).Biological reactivity:Implantable and combination drug products (drug/device) that contain a polymeric material should meet the requirements of Biological Reactivity Tests, In Vivo á88ñ.Globule size distribution:Emulsions should meet the requirements of Globule Size Distribution in Lipid Injectable Emulsionsá729ñ.Aluminum content:Large-volume parenterals used to make total parenteral nutrition therapy (TPN) are limited to 25 m g/L. Small-volume parenterals and pharmacy bulk packages used to make TPN must state on the immediate container label the maximum level of aluminum at expiry if the maximum level exceeds 25 m g/L.Completeness and clarity of solutions:The following tests are performed to demonstrate suitability of constituted solutions prepared before administration. Constitute the solution as directed in the labeling supplied by the manufacturer:•The solid dissolves completely, leaving no undissolved matter.•The constituted solution is not significantly less clear than an equal volume of the diluent or of Purified Water contained in a similar vessel and examined similarly. Protein solutions may exhibit an inherent opalescence.The constituted solution is free from particulate matter that can be observed on visual inspection (see Visible Particulates in Injections á790ñ).PRODUCT QUALITY TESTS FOR SPECIFIC PARENTERAL DOSAGE FORMSProduct quality tests for the specific dosage forms are listed below. Specific chapter(s) referenced for the test can be found in the Universal Tests and Specific Tests sections. When there is no compendial test available, a validated procedure with accept-ance criteria should be used.SolutionsA solution is a clear, homogeneous liquid dosage form that contains one or more chemical substances (e.g., drug substances or excipients) dissolved in a solvent (aqueous or nonaqueous) or a mixture of mutually miscible solvents. Solutions intended for parenteral administration (e.g., by injection or for irrigation) must be sterile and biocompatible with the intended adminis-tration site. This includes consideration of factors such as tonicity, pH, pyrogenicity, extraneous particulate matter, and physi-cochemical compatibility, among others.Unless otherwise justified, the following tests are required for solutions for injection:•Universal Tests•Specific Tests—Physicochemical Properties: Specific Gravity, Viscosity, pH, Osmolarity and Osmolality—Antimicrobial Preservatives Sterile Powders for SolutionSterile powders for solutions (also referred to as sterile powders for injection) consist of drug substances and other compo-nents as dry-formulation ingredients to ensure the chemical and physical stability of the presentation within a final-use con-tainer. Companion sterile diluent or diluent compartments may be provided to facilitate constitution to the desired final vol-ume.The sterile article for injection may be presented in several forms: lyophilized powder intended for final solution, powdered solids intended for final solution, or dry solids that form viscous liquids upon constitution.The description should include a section that deals with ease of dispersion and reconstitution. The dosage form is a homoge-neous solid that is readily constituted to the final form with the specified diluent, and dispersion is completed with gentle agi-tation.Unless otherwise justified, the following tests apply to sterile powders for injection:•Universal Tests•Specific Tests—Physicochemical Properties: Specific Gravity, Viscosity, pH, Osmolarity and OsmolalityThe following applies to constituted solutions:•Uniformity of Dosage Units á905ñ: To ensure the consistency of dosage units, each unit in a batch should have a drug sub-stance content within a narrow range around the label claim. Dosage units are defined as dosage forms that contain a single dose or a part of a dose of drug substance in each unit. For liquid dosage forms analysts should conduct the assay on an amount of well-mixed constituted material that is removed from an individual container under conditions of normal use, should express the results as delivered dose, and should calculate the acceptance value.•Loss on Drying á731ñ: The procedure set forth in this chapter determines the amount of volatile matter of any kind that is driven off under the conditions specified.•Water Determination á921ñ: Water or solvent content may have important effects on reconstitution and stability. For arti-cles that require water or solvent content control, analysts should perform one of the following methods or a suitable re-placement.•Appearance : Analysts should assess the level of and the unit variation for the following parameters:—Color of Cake: Varies within target parameters—Texture and Homogeneity of Cake: Varies within target parameters—Presence of Foreign Material: All units with visible foreign material must be rejected—Particle Size and Distribution (Dry Powder): Evaluation of the powder solids for proper solid form and crystallinity is a measure of process control and consistency.•Particle Size Distribution Estimation by Analytical Sieving á786ñ: This chapter can be used for loose powders.Crystallinity:The crystallinity of a material can be characterized to determine compliance with the crystallinity requirementwhere stated in the individual monograph of a drug substance.•Optical Microscopy á776ñ: Crystallinity can be characterized by polarized light microscopy for qualitative evaluation of the size, shape, and crystallinity of solids. Unless otherwise specified in the individual monograph, analysts should mount a solid specimen in mineral oil on a clean glass slide or cover slip and should examine the mixture using a polarizing micro-scope: The particles show birefringence (interference colors) and extinction positions when the microscope stage is re-volved.Vehicles and diluents:Guidelines for constitution and suspension of dry powders are found in the specific monographs. If there is a specific packaged diluent for use with a particular product that is not included in a monograph, then the final article is prepared with that diluent.SuspensionsParenteral suspensions are liquid dosage forms that contain solid particles in a state of uniform dispersion. Suspensions for parenteral administration must be sterile and compatible with the administration site. Consideration should be given to pH and pyrogenicity, and appropriate limits should be identified. Physical stability evaluations of parenteral suspension prepara-tions should include evaluations to confirm that the particle size range of suspended matter does not change with time and to confirm that the solids in the preparation can be readily resuspended to yield a uniform preparation.In addition to the tests for injectable solutions, the following tests are required for suspensions for injection unless otherwise justified:•Universal Tests•Specific Tests—Physicochemical Properties: pH—Uniformity of Dosage Units—Antimicrobial PreservativesLiposomesLiposomes are unique drug products with unique properties that can be either solutions or suspensions. Liposomes are aqueous dispersions of amphiphilic lipids and have low water solubility. They are organized as a bilayer sheet that encloses an internal aqueous compartment and are known as lipid bilayer vesicles. Liposomes can have a single lipid bilayer (unilamellar vesicle) or can have an onion-like multilayered structure (multilamellar vesicle). The amphiphilic lipids comprise a hydrated head group at the water interface of the bilayer attached to a hydrophobic group that forms the interior of the bilayer by asso-ciation with the hydrophobic group of lipids from the opposite leaflet of the bilayer. The physical properties of the liposome and its bilayer can vary widely and depend on lipid composition, aqueous composition, and temperature relative to the acyl components' phase transition points. Because of the central aqueous compartment, a simple test for the presence of liposomes in a lipid dispersion is to determine the presence of an entrapped aqueous phase.A liposome drug product consists of the drug substance, liposome components, and other inactive but critical ingredients such as an aqueous dispersion unless the contents are a lyophilized product.Unless otherwise justified, the following tests are required for liposomes:•Universal Tests•Specific Tests—Physicochemical Properties: pH—Lipid and Fatty Acid Composition, including degree of unsaturation and positional specificity in acyl side chains and critical degradation products such as lysolipids2—Particle Size2—Particle Size Distribution of Liposomal Vesicles2—Lamellarity2—Phospholipid Composition2—Percent Free vs. Percent Encapsulated Lipids2—Free Drug vs. Encapsulated Drug—Ionic Strength and Osmotic Strength2Sterile Powders for SuspensionSterile powders for suspensions consist of drug substances and other components as dry-formulation ingredients to ensure the chemical and physical stability of the presentation within a final-use container. Companion sterile diluent or diluent com-partments may be provided to facilitate constitution to the desired final volume.The sterile article for injection may be presented in several forms: lyophilized powder intended for final suspension, pow-dered solids intended for final suspension, and microparticles that retain their integrity and are delivered as a sterile suspen-sion. The description should include a section that deals with ease of dispersion and reconstitution. The dosage form is a ho-2No compendial test available; a validated procedure with acceptance criteria should be used.mogeneous solid that is readily constituted to the final form with the specified diluent, and dispersion is completed with gentle agitation.Unless otherwise justified, the following tests apply to sterile powders for injection:•Universal Tests•Specific Tests•Bacterial Endotoxins—Physicochemical Properties: pH, Osmolarity and OsmolalityThe following applies to constituted suspensions:•Uniformity of Dosage Units á905ñ: To ensure the consistency of dosage units, each unit in a batch should have a drug sub-stance content within a narrow range around the label claim. Dosage units are defined as dosage forms that contain a single dose or a part of a dose of drug substance in each unit. For liquid dosage forms, analysts should conduct the assay on an amount of well-mixed constituted material that is removed from an individual container under conditions of normal use, should express the results as delivered dose, and should calculate the acceptance value.•Loss on Drying á731ñ: The procedure set forth in this chapter determines the amount of volatile matter of any kind that is driven off under the conditions specified.•Water Determination á921ñ: Water or solvent content may have important effects on reconstitution and stability. For arti-cles that require water or solvent content control, analysts should perform one of the following methods or a suitable re-placement.•Appearance : Analysts should assess the level of and the unit variation for the following parameters:—Color of Cake: Varies within target parameters—Texture and Homogeneity of Cake: Varies within target parameters—Presence of Foreign Material: All units with visible foreign material must be rejected—Particle Size and Distribution (Dry Powder): Evaluation of the powder solids for proper solid form and crystallinity is ameasure of process control and consistency.•Particle Size Distribution Estimation by Analytical Sieving á786ñ: This chapter can be used for loose powders.Crystallinity:The crystallinity of a material can be characterized to determine compliance with the crystallinity requirement where stated in the individual monograph of a drug substance.•Optical Microscopy á776ñ: Crystallinity can be characterized by polarized light microscopy for qualitative evaluation of thesize, shape, and crystallinity of solids. Unless otherwise specified in the individual monograph, analysts should mount a solid specimen in mineral oil on a clean glass slide or cover slip and should examine the mixture using a polarizing micro-scope: The particles show birefringence (interference colors) and extinction positions when the microscope stage is re-volved.Vehicles and diluents:Guidelines for constitution and suspension of dry powders are found in the specific monographs. If there is a specific packaged diluent for use with a particular product that is not included in a monograph, then the final article is prepared with that diluent.Microparticles:Some microparticles are provided as a sterile powder to be reconstituted as a suspension before injection.Major microparticle preparations are for reconstitution as a suspension for injection. For quality test requirements, please refer to Implants .EmulsionsEmulsions for parenteral dosage forms are liquid preparations of drug substances dissolved or dispersed in a suitable emul-sion medium. Oil-in-water or water-in-oil emulsions typically entrap the drug substance.Emulsions typically are white, turbid, homogeneous liquid dosage forms that contain one or more chemical substances (e.g.,drug substances and excipients) dissolved in a solvent (aqueous or nonaqueous) or mixture of mutually miscible solvents.Emulsions intended for intravenous administration must be sterile and must be compatible with the intended administration site.Unless otherwise justified, the following tests are required for emulsions for injection:•Universal Tests•Specific Tests—Physicochemical Properties: pH, Osmolarity and Osmolality—Globule Size Distribution—Amount of Fat Globules (lipids)2—Percent Free vs. Percent Encapsulated Lipids 2—Free Drug vs. Encapsulated DrugImplantsImplants for extended release consist of a matrix of drug substance and polymeric excipient that may or may not have an outer rate-controlling membrane. The polymeric excipient must be biocompatible but may or may not be bioresorbable.Some implants are made from medical-grade metal with an osmotic pump inside that effects the extended release of the drug。
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。
化验知识2010版药典注射剂通则
类别
可见异物限度
化学药
生化药、抗生 ≥2g 素药和中药
≤4个 ≤10个
<2g
≤8个
可见异物
无菌原料药 5份检查的供试品中，均不得检出明显可 见异物。如检出微细可见异物，每份供试品中检出微 细可见异物的数量应符合下表的规定；如有 1份不符 合规定，另取10份同法复试，均应符合规定。
既可静脉用也可非静脉用的注射剂应执行静脉用注射 剂的标准。
临用前配制的溶液型和混悬型滴眼液，除另有 规定外，应符合相应的可见异物规定。
可见异物
注射用无菌粉末 被检查的5支〔瓶〕供试品中，均不得检出明 显可见异物。如检出微细可见异物，每支〔瓶〕供试品中检出
微细可见异物的数量应符合下表的规定；如有1支〔瓶〕不符 合规定，另取10支〔瓶〕同法复试，均应符合规定。配带有专 用溶剂的注射用无菌粉末，专用溶剂应符合相应的溶液型注射
用的无菌浓溶液。
二：注射剂的质量要求
①溶液型注射液应澄明。乳状液型注射 液应稳定，不得有相别离现象，不得用 于椎管注射。除另有规定外，静脉输液 应尽可能与血液等渗。
注射剂的质量要求
② 注射剂所用的原辅料应从来源及工艺等生产 环节进展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平安无害，不影响疗效和 质量，一般分为水性溶剂和非水性溶剂。
注射剂检验通那么
2021年版
一. 概述
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 。
注射剂分类
一：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，供静脉滴注用的大体积〔除 另有规定外，一般不小于100ml〕注射 液也称静脉输液。
欧洲药典泡沫剂通则-概述说明以及解释
欧洲药典泡沫剂通则-概述说明以及解释1.引言1.1 概述欧洲药典泡沫剂通则是药品行业中一项重要的标准和规范，旨在确保泡沫剂的质量和安全性。
泡沫剂作为一种常见的药剂制剂形式，广泛用于皮肤疾病治疗、伤口愈合和消毒等领域。
本文旨在介绍欧洲药典泡沫剂通则的主要内容和其在泡沫剂行业中的重要性。
首先，将介绍欧洲药典泡沫剂通则的背景，包括制定该通则的原因和背景资料。
其次，会详细阐述泡沫剂的定义和分类，包括其成分、制备方法以及应用范围等方面的内容。
文章还将重点讨论欧洲药典泡沫剂通则对于泡沫剂行业的影响和展望。
引入该通则后，泡沫剂行业将更加严格地遵循一系列可行的制剂方法和规范要求，以确保产品的质量和稳定性。
同时，泡沫剂行业也将受益于通则的指导，提高产品的竞争力和市场认可度。
综上所述，欧洲药典泡沫剂通则在泡沫剂行业中具有重要的意义。
通过规范化制剂方法和质量要求，该通则为泡沫剂行业的发展注入了新的活力，并促进了行业的良性竞争和创新。
1.2 文章结构文章结构部分的内容可以包括以下方面：文章结构部分应该在引言部分之后，用于介绍整篇文章的组织架构和章节安排。
通过清晰明了地列出文章的各个章节，读者可以更好地理解文章的逻辑结构，把握文章的脉络。
在本文中，文章结构部分可以按照如下方式编写内容：文章结构部分应该包括每个章节的序号和名称，并简要介绍每个章节的主要内容和要点。
2. 正文部分将详细介绍欧洲药典泡沫剂通则的背景信息和泡沫剂的定义和分类。
2.1 欧洲药典泡沫剂通则的背景部分将介绍该通则的产生背景、目的和意义。
2.2 泡沫剂的定义和分类部分将详细说明泡沫剂的概念和定义，并按照其性质、用途、成分等方面进行分类和归类。
3. 结论部分将总结和归纳文章的主要观点和结论。
3.1 欧洲药典泡沫剂通则的重要性部分将说明该通则对泡沫剂行业以及相关领域的重要意义和影响。
3.2 对泡沫剂行业的影响和展望部分将展望该通则对泡沫剂行业发展的影响，并提出一些个人的思考和看法。
欧洲药典注射用水检验规程
目的使注射用水的检验操作标准化、规范化，保证注射水的质量，从而保证产品质量。
范围适用于注射用水的检验职责由化验室起草；部门经理及相关人员审核；质量总监批准；化验员执行。
内容1编制依据EP7.02定义通常用作溶剂(散装注射用水)来溶解、稀释物质或作为非肠道注射准备用水(无菌注射用水)的药物非肠道给药的准备用水3执行标准《注射用水质量标准》。
4性状本品为无色的澄明液体。
5检查5.1硝酸盐5.1.1仪器与装置：量筒、试管、移液管、水浴锅。
5.1.2试剂与试液：标准硝酸盐溶液、10%氯化钾溶液、0.1%二苯胺硫酸溶液、硫酸。
标准硝酸盐溶液：取硝酸钾0.163g，加水溶解并稀释至100ml，摇匀，再精密量取1ml，加水稀释成100ml，摇匀，再精密量取20ml，加水稀释成100ml，摇匀，即得（每1ml相当于2μgNO3-）。
5.1.3测定方法：取本品5ml置试管中，于冰浴中冷却，加10%氯化钾溶液0.4ml与0.1%二苯胺硫酸溶液0.1ml，摇匀，缓缓滴加无氮硫酸5ml，摇匀，将试管于50℃水浴中放置15分钟，溶液产生的蓝色与标准硝酸盐溶液（2ppm NO3），加无硝酸盐的水4.5ml，用同一方法处理后的颜色对比，不得更深。
5.1.4结果判定：不超过0.2ppm。
5.2电导率5.2.1电导计：最低限的分辨率为0.1μS·cm-1，准确度：±3%，温度测量：±2℃。
5.2.2步骤阶段一1.用非温度补偿或温度补偿的电导仪测定水的温度和电导率，在适当的容器中测量或在线测量。
2.在表0169- 2中找到最接近的温度的值不能大于实测温度。
以相应的温度电导率值为限值。
3.如果测量电导率不大于表0169-2中的值，则水要符合表0169-2中的电导率限值。
如果电导率高于表0169-2中的值则继续进行阶段二。
表0169-2. -温度和电导率要求（非温度补偿电导率测量）温度（℃）电导率（μS·cm-1）0 0.6 5 0.8 10 0.9 15 1.0 20 1.130 1.435 1.540 1.745 1.850 1.955 2.160 2.265 2.470 2.575 2.780 2.785 2.790 2.795 2.9100 3.1阶段二4.取至少100毫升样品到一个合适的容器中，搅拌样品。
中美欧药典注射剂通则比对.pdf
三 溶剂和添加剂
• 不 皂 化 物 - 脂肪油 10ml 与 氢氧 化 钠 溶液 （1→6）15ml 和乙醇30ml蒸汽浴回 流，时时 振摇直至混合物澄清。将溶液转移到平皿，蒸 汽浴上挥去乙醇 ，残渣加水100ml，应生成澄 清的溶液。
• 游离脂肪酸 -用于中和10g脂肪油中的游离脂肪 酸所需 的 0.020N 氢氧 化 钠 溶液 不得过 2.0ml （见脂肪和脂肪油<401>）
三 溶剂和添加剂
• 添加剂-为提高稳定性和方便使用，注射 用制剂中可加 入适当的物质，这些物质 应在该药量下 无害，不影响疗 效，不干 扰规定的含量 测定和 检查 。肠道 外给药 的溶液中 不得 添加仅 为对最终 制剂 着色 的着色 剂（并见 凡例 中的添加剂项和 附 录抗菌效率检查<51>）。
三 溶剂和添加剂
一定义
• USP术语和定义 • NOMENCLATURE AND DEFINITIONS • 术语和定义 • Nomenclature* • 术语
•. • 下列术语适用于5种注射给药的一般剂型。这些制剂
可能含有缓冲剂、防腐剂或其他添加剂。
一定义
• 1．[药物]注射液- 药物或其溶液的液体制剂。 • 2．注射用[药物]- 干固体，加适宜溶剂制成的溶液符合
• Vehicles and Added Substances
• 成分
• 溶剂和添加剂
欧洲药典泡沫剂通则
欧洲药典泡沫剂通则全文共四篇示例，供读者参考第一篇示例：欧洲药典是欧洲最具权威性的药典之一，其中有关泡沫剂的通则是药品制备和使用的重要指导。
泡沫剂是一种含有气泡或气体的液体剂型，通常用于治疗皮肤疾病或创伤。
在欧洲药典中，泡沫剂的制备和质量控制有着严格的要求，以确保药品的安全和有效性。
根据欧洲药典的规定，泡沫剂的制备应当在符合GMP（良好生产规范）的条件下进行。
在制备泡沫剂时，必须严格控制原材料的质量，比如洗净水、表面活性剂、推进剂、保存剂等均必须符合药典规定。
必须对泡沫剂的配方和制备过程进行充分验证，确保药品的稳定性和安全性。
欧洲药典还对泡沫剂的质量控制提出了严格要求。
泡沫剂应该具有合适的稳定性，能够在存储和使用过程中保持其外观和性能。
药品中气泡的分布应均匀，泡沫的大小和气泡的密度也应符合药典标准。
泡沫剂的pH值、抗菌活性、粘度等质量指标也需要定期检测和监控。
在欧洲药典的泡沫剂通则中，还规定了泡沫剂的使用方法和注意事项。
使用泡沫剂时，应该根据药品说明书中的指导进行使用，避免过量使用或长时间使用。
在使用泡沫剂时要注意眼部、口腔等敏感部位的避开，避免药品误入眼睛或口腔引起不良反应。
欧洲药典的泡沫剂通则为制备、质量控制和使用泡沫剂提供了重要指导。
遵循药典规定，可以确保泡沫剂的质量和安全性，有效地治疗皮肤疾病和创伤，提高患者的治疗效果和生活质量。
欧洲药典的泡沫剂通则也为药品生产企业和医疗机构提供了规范，促进行业良性发展。
第二篇示例：欧洲药典泡沫剂通则指导着在欧洲市场上生产和销售泡沫剂的相关企业。
泡沫剂是一种常见的药物剂型，用于外用药物的发挥作用。
欧洲药典泡沫剂通则明确了生产泡沫剂所需遵循的法规标准、质量要求、生产流程等方面的规定，以确保泡沫剂的安全性、有效性和质量一致性。
泡沫剂是一种含气剂型，通过压缩气体或其他推进剂将药物喷射出来，在患处形成泡沫，在患处留下足够的时间以实现所需的治疗效果。
泡沫剂具有易于使用、易于吸收、不易流失等优点，因此在各种外用药物中得到广泛应用。
欧洲药典7.0-凡例(全)
07/2010:10000 1. 凡例1.1. 概述凡例的内容适用于各论和欧洲药典中的其它章节。
欧洲药典以英语和法语形式发行，欧洲药典委员会的签署国可将药典内容译成其它语言，但若发生争议，应以英语和法语版为权威。
在欧洲药典中，如无特殊规定，“药典”是指欧洲药典，官方缩写Ph. Eur.也指欧洲药典。
文章中如果引用了各论中的标题和副标题意味着文章内容符合相关各论的要求。
文章参考药典中各论内容时，以斜体的各论题目或相关数字表示。
制剂在有效期内必须性质稳定，明确的有效期或说明书应由权力机构批准。
任何各论的物质也必须服从其使用期限。
任何药品的有效期和有效期的计算由权力机构经稳定性研究的试验结果决定。
除凡例和各论中另有说明，各论中的说明为强制要求；除了特定的引用信息，如果各论引用总论中内容时，该总论要求为法定要求。
各论中描述的活性物质，赋形剂，药物制剂和其它项目都是人用和兽用的（除非明确限制不可使用）。
药品项目必须符合各论的要求，否则不符合药典质量。
但并不要求产品放行前，生产商要做各论中的每项试验以满足药典要求。
生产商可通过原始数据，例如生产过程验证，和中间体控制，确保药品是否符合药典要求。
公布的环境参数，权力机构可适当采信，但不排除故意满足药典要求的可能。
检测和试验方法应基于药典标准的官方方法。
经权利机构允许可采用其它替代的分析方法以达到控制目的，并证明该方法是否能达到各论各标准。
若出现争论或异议，应以药典方法为准。
药典各论中的某些物质有多个等级可满足各种需要，除各论中另有说明，要求适用于各等级。
在一些各论中，特别是赋形剂，一系列相关的功能特性都有介绍，其中给出了一些特性的检测方法。
质量体系：在适宜的质量体系架构下，产生有疑问的项目时，应以各论中的质量标准为法定标准。
通则：各论中介绍的药物和制剂也应符合通则中的相关要求。
交叉引用的通则在各论中不特别指出。
除非限定了适用条件，如规定适用于药典各论中的物质，通则的内容适用于各论定义范围内的所有药物和制剂。
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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。