USP905含量均匀度中英文

1、<905> UNIFORMITY OF DOSAGE UNITSContent UniformityThe test for Content Uniformity is based on the assay of the individual content of drug substance(s) in a number of individual dosage units to determine whether the individual content is within the limits set. The Content Uniformity method may

2、be applied in all cases. The test for Content Uniformity is required for those dosage forms described in (C1)(C6) below:(C1) coated tablets, other than film-coated tablets containing 25 mg or more of a drug substance that comprises 25% or more (by weight) of one tablet.(C2) transdermal systems(C3) s

3、uspensions or emulsions or gels in single-unit containers or in soft capsules that are intended for systemic administration only (not for those drug products that are intended for topical administration);(C4) inhalations (other than solutions for inhalation packaged in glass or plastic ampuls and in

4、tended for use in nebulizers) packaged in premetered dosage units. For inhalers and premetered dosage units labeled for use with a named inhalation device, also see Aerosols, Nasal Sprays, Metered-Dose Inhalers, and Dry Powder Inhalers <601>(C5) solids (including sterile solids) that are packa

5、ged in single-unit containers and that contain active or inactive added substances, except that the test for Weight Variation may be applied in the special cases stated in (W3) below; and(C6) suppositoriesSelect not fewer than 30 units, and proceed as follows for the dosage form designated. Where th

6、e amount of drug substance in a single dosage unit differs from that required in the Assay, adjust the degree of dilution of the solutions and/or the volume of aliquots so that the concentration of the drug substances in the final solution is of the same order as that obtained in the Assay procedure

7、; or, in the case of a titrimetric assay, use a titrant of a different concentration, if necessary, so that an adequate volume of titrant is required (see Titrimetry <541>); see also Procedures under Tests and Assays in the General Notices and Requirements. If any such modifications are made i

8、n the Assay procedure set forth in the individual monograph, make the appropriate corresponding changes in the calculation formula and titration factor.Where a special Procedure for content uniformity is specified in the test for Uniformity of dosage units in the individual monograph, make any neces

9、sary correction of the results obtained as follows.1. Prepare a composite specimen of a sufficient number of dosage units to provide the amount of specimen called for in the Assay in the individual monograph plus the amount required for the special Procedure for content uniformity in the monograph b

10、y finely powdering tablets or mixing the contents of capsules or oral solutions, suspensions, emulsions, gels, or solids in single-unit containers to obtain a homogeneous mixture. If a homogeneous mixture cannot be obtained in this manner, use suitable solvents or other procedures to prepare a solut

11、ion containing all of the drug substance, and use appropriate aliquot portions of this solution for the specified procedures. 2Assay separate, accurately measured portions of the composite specimen of capsules or tablets or suspensions or inhalations or solids in single-unit containers, both (a) as

12、directed in the Assay, and (b) using the special Procedure for content uniformity in the monograph. 3Calculate the weight of drug substance equivalent to 1 average dosage unit, by (a) using the results obtained by the Assay procedure, and by (b) using the results obtained by the special procedure. C

13、alculate the correction factor, F, by the formula: F = W/P in which W is the weight of drug substance equivalent to 1 average dosage unit obtained by the Assay procedure, and P is the weight of drug substance equivalent to 1 average dosage unit obtained by the special procedure. If is greater than 1

14、0, the use of a correction factor is not valid. 5The correction factor is to be applied only if F is not less than 1.030 nor greater than 1.100, or not less than 0.900 nor greater than 0.970. If F is between 0.970 and 1.030, no correction is required. 6If F lies between 1.030 and 1.100, or between 0

15、.900 and 0.970, calculate the weight of drug substance in each dosage unit by multiplying each of the weights found using the special procedure by F. Uncoated, Coated, or Molded Tablets, Capsules, Oral Solutions in Unit-Dose Containers, Suspensions or Emulsions or Gels in Single-Unit Containers (tha

16、t are intended for systemic administration only), and Solids (including Sterile Solids) in Single-Unit Containers Assay 10 units individually as directed in the Assay in the individual monograph, unless otherwise specified in the Procedure for content uniformity in the individual monograph. Calculat

17、e the acceptance value as directed below. For oral solutions in unit-dose containers, and for suspensions, emulsions, or gels in single-unit containers that are intended for systemic administration only, conduct the Assay on the amount of well-mixed material that drains from an individual container

18、in not more than 5 seconds, or for highly viscous products, conduct the Assay on the amount of well-mixed material that is obtained by quantitatively removing the contents from an individual container, and express the results as the delivered dose.Calculation of Acceptance Value Calculate the accept

19、ance value by the formula: Suppositories, Transdermal Systems, and Inhalations Packaged in Premetered Dosage Units noteAcceptance value calculations are not required for these dosage forms. Assay 10 units individually as directed in the Assay in the individual monograph, unless otherwise specified i

20、n the Procedure for content uniformity. 含量均匀度建立在通过测定一定数量的单个剂量的原料药单个含量来确定单个含量是否符合限度要求。含量均匀度测试方法可以应用于所有的情况下。以下六种剂型要求测定含量均匀度：(C1) 包衣片，除了含有25mg或更多原料药的薄膜包衣片，其原料药组成占了片剂总重的25%。(C2) 经皮系统(C3) 单个剂量包装的或用仅于全身给药（而不是局部给药）的软胶囊包装的混悬剂或乳剂或凝胶剂。(C4) 包装于单位计量进过事先测量的过吸入剂（除了包装于玻璃或塑料安瓿中用于喷雾的溶液剂）。对于标签上标注需要使用到指定的吸入器的吸入剂和事先测量过

21、单位剂量，可参见喷雾器，鼻喷雾器，定量吸入剂和干粉吸入剂<601>。(C5) 包装于单个剂量容器中固体（包括无菌固体），含有活性或无活性的添加剂，除了重量差异的测试中可以应用于(W3)所列举的特殊情况。(C6) 栓剂选择不少于30个单位，按照剂型指定的操作进行。当单剂量中原料药的量与含量测定中所要求的不同时，调整溶液稀释的程度以及等份的体积使得最终得到溶液中含有的原料药浓度与含量测定中的浓度在一个数量级上；再如在滴定的含量测定中，必要时使用不同浓度的滴定液以得到合适的体积。（参见滴定<541>）;也可以参见总体注意事项中测试法和含量测定。如果在各论中关于含量测定法有任何

22、的修改，要对计算公式和滴定因子进行相应的改变。当各论中指定了特殊的含量均匀度测定法时，按下述方法对结果做任何必要的修正。1准备足够数量的剂量单位的复合样本来提供给各论中含量测定以及各论中含量均匀度测定测试法项下特殊的数量要求用，这些测试法需要将片剂磨成粉末或是将单个包装的胶囊、口服液体制剂、混悬剂、乳剂、凝胶剂或固体制剂中内容物混合得到均一的混合物。如果不能通过上述方法得到均一的混合物，使用合适的溶剂或其它的方法来制备含有所有药物的溶液，并使用合适的溶液等份来为指定的测试法制备供试品。2对准确测量的单个包装的胶囊、片剂、混悬剂、吸入剂或固体制剂复合样品进行单独的测定，（1）按照含量测定方法；（

23、2）按照各论中含量测定测试法项下的方法。3通过下面两种方法计算等量于平均单剂量的药物的重量，（1）使用含量测定法得到的结果；（2）使用特殊测试法得到的结果。计算校正因子F公式为：F = W/PW指通过含量测试法中得到的相当于平均单剂量的药物重量；P 通过特殊测试法中得到的指相当于平均单剂量的药物重量。如果：的值大于10，使用这个校正因子是无效的。5校正因子只适用于F不小于1.030且不大于1.100的情况，或者是不小于0.900且不大于0.970的情况。如果F在0.970和1.030之间，不需要使用校正。6如果F在1.030和1.100之间，或在0.900和0.970之间，特殊测试法中得到的原

24、料药的重量要与F相乘来计算每一个单剂量原料药的重量。非包衣、包衣、压膜片、胶囊、单剂量包装的口服溶液、单剂量包装的混悬剂、溶剂、凝胶剂（仅用于全身系统给药）和单包装的固体制剂（包括无菌固体制剂）在各论中含量测定项下取10个单位剂量进行检测，除非各论中含量均匀度测定法项下有另行规定。按照下述方法计算AV值。对于仅用于系统全身给药的单剂量包装中的口服液体制剂，以及单剂量包装的混悬剂、乳剂或凝胶剂， 在进行测定时，从单独容器中滤干得到充分混匀的物料的含量测定不得超过5s。高粘度的产品在进行含量测定时，定量的转移单个容器中的内容物来得到混合均匀的无聊进行含量测定，所得到的结果为可转移的剂量。AV的计算

25、按照下面的公式：包装于事先定量的剂量单位的栓剂，透皮系统，吸入剂注意：这些剂型不需要进行AV值的计算。对10个单位进行单独的含量测定，按照各论中含量测定指示的方法，除非在含量均匀度测定的测试法项下有另行规定。Weight VariationThe test for Weight Variation is applicable for the following dosage forms:(W1) solutions for inhalation that are packaged in glass or plastic ampuls and intended for use in nebuli

26、zers, and oral solutions packaged in unit-dose containers and into soft capsules;(W2) solids (including sterile solids) that are packaged in single-unit containers and contain no added substances, whether active or inactive;(W3) solids (including sterile solids) that are packaged in single-unit cont

27、ainers, with or without added substances, whether active or inactive, that have been prepared from true solutions and freeze-dried in the final containers and are labeled to indicate this method of preparation; and(W4) hard capsules, uncoated tablets, or film-coated tablets, containing 25 mg or more

28、 of a drug substance comprising 25% or more, by weight, of the dosage unit or, in the case of hard capsules, the capsule contents, except that uniformity of other drug substances present in lesser proportions is demonstrated by meeting Content Uniformity requirements.重量差异测试应用于以下剂型：(W1) 包装于玻璃或塑料安瓿中用于

29、喷雾吸入的溶液剂，和包装于单位剂量容器中与软胶囊中口服给药溶液剂。(W2) 包装于单个剂量容器中的固体（包括无菌固体），不含有添加剂，无论是活性的还是无活性的。(W3) 包装于单个剂量的容器中含有或不含有添加物质的固体（包括无菌固体），添加物质可以具有活性也可以是无活性的。固体制剂通过真溶液和在最终容器中冻干进行制备，并且标签中指定了此种制备方法。(W4) 硬胶囊，未包衣片或薄膜包衣片，含有25mg或更多的原料药，原料药占剂量单位重量的的25%或更多，胶囊的内容物。其它比例更少的原料药均匀度需要证明其符合含量均匀度要求。The test for Content Uniformity is re

30、quired for all dosage forms not meeting the above conditions for the Weight Variation test.Where compliance with the Content Uniformity test is required, then, by application of the provision for use of alternative methods provided in the General Notices section of this Pharmacopeia, it is possible

31、for manufacturers to ensure this compliance by application of the Weight Variation test where the concentration relative standard deviation (RSD) of the drug substance in the final dosage units is not more than 2%. This RSD determination may be based on the manufacturer's process validation and

32、product development data. The concentration RSD is the RSD of the concentration per dosage unit (w/w or w/v), where concentration per dosage unit equals the assay result per dosage unit divided by the individual dosage unit weight. See the RSD formula in Table 2. Where the Weight Variation test is u

33、sed in this way, the product must, if tested, nevertheless comply with the official compendial test for Content Uniformity.Select not fewer than 30 dosage units, and proceed as follows for the dosage form designated. The result of the Assay, obtained as directed in the individual monograph, is desig

34、nated as result A, expressed as % of label claim (see Calculation of Acceptance Value). Assume that the concentration (weight of drug substance per weight of dosage unit) is uniform. noteSpecimens other than these test units may be drawn from the same batch for assay determinations. Uncoated or Film

35、-Coated Tablets Accurately weigh 10 tablets individually. Calculate the drug substance content, expressed as % of label claim, of each tablet from the weight of the individual tablet and the result of the Assay. Calculate the acceptance value. Hard Capsules Accurately weigh 10 capsules individually,

36、 taking care to preserve the identity of each capsule. Remove the contents of each capsule by a suitable means. Accurately weigh the emptied shells individually, and calculate for each capsule the net weight of its contents by subtracting the weight of the shell from the respective gross weight. Cal

37、culate the drug substance content, expressed as % of label claim, of each capsule from the net weight of the individual capsule content and the result of the Assay. Calculate the acceptance value. Soft Capsules Accurately weigh 10 intact capsules individually to obtain their gross weights, taking ca

38、re to preserve the identity of each capsule. Then cut open the capsules by means of a suitable clean, dry cutting instrument such as scissors or a sharp open blade, and remove the contents by washing with a suitable solvent. Allow the occluded solvent to evaporate from the shells at room temperature

39、 over a period of about 30 minutes, taking precautions to avoid uptake or loss of moisture. Weigh the individual shells, and calculate the net contents. Calculate the drug substance content, expressed as % of label claim, in each capsule from the net weight of product removed from the individual cap

40、sules and the result of the Assay. Calculate the acceptance value. Solids (Including Sterile Solids) in Single-Unit Con tainers Proceed as directed for Hard Capsules, treating each unit as described therein. Calculate the acceptance value. Oral Solutions Packaged in Unit-Dose Containers Accurately w

41、eigh the amount of liquid that drains in not more than 5 seconds from each of 10 individual containers. If necessary, compute the equivalent volume after determining the density. Calculate the drug substance content, expressed as % of label claim, in the liquid drained from each unit from the net we

42、ight of the individual container content and the result of the Assay. Calculate the acceptance value. Calculation of Acceptance Value Calculate the acceptance value as shown in Content Uniformity, except that the individual contents of the units are replaced with the individual estimated contents de

43、fined below. 1, 2, , n = individual estimated contents of the units tested, where i = Wi ×A /W1, W2, , Wn = individual weights of the units tested, for weight variation,A = content of drug substance (% of label claim) determined as described in the Assay W = mean of individual weight (W1, W2, ,

44、 Wn) of the units used in the Assay. Solutions for Inhalation Packaged in Glass or Plastic Ampuls and Intended for Use in Nebulizers noteAcceptance value calculations are not required for these dosage forms. Accurately weigh 10 containers individually, taking care to preserve the identity of each co

45、ntainer. Remove the contents of each container by a suitable means. Accurately weigh the emptied containers individually, and calculate for each container the net weight of its contents by subtracting the weight of the container from the respective gross weight. From the results of the Assay, obtain

46、ed as directed in the individual monograph, calculate the drug substance content, expressed as % of label claim, in each of the containers. 不满足以上重量差异测试要求的所有剂型需要进行含量均匀度测试。当需要符合含量均匀度测试要求时，可以应用总体注意事项中替代方法的使用要求。在最终剂型单位的原料药浓度相对标准偏差不超过2%的情况下，生产商可以应用重量差异测试保证符合含量均匀度测试要求。RSD的测定可以根据生产商的过程验证和药物开发数据来确定。在每剂量单位浓度

47、等于以按照重量划分的每剂量单位含量测定结果时，浓度RSD指的是每个剂量单位（w/w, 或w/v）的浓度的RSD。参见表2中RSD公式。当重量差异测试按照这种方法使用时，如果进行含量均匀度测试，产品必须符合官方药典中含量均匀度测试的要求。选择不少于30个剂量单位，按照下列指定的剂型进行测定。按照各论中指示得到的含量测定的结果被指定为结果A，表述为标示量的百分含量（参见AV值的计算）。假定浓度（每剂量单位的原料药的重量）是均一的。非包衣或薄膜包衣片剂准确逐一称量10片片剂的重量。计算原料药的含量，表述为每一个片剂标示量或每一片单独片剂重量的百分含量以及含量测定的结果。计算AV值。硬胶囊准确称量10

48、个胶囊的单个重量，确保每一个胶囊与其重量的对应关系。使用适当的方法移取每一个胶囊的内容物。准确称量每一个胶囊空壳，通过从各自的总重量减去胶囊空壳的重量计算每一个胶囊的内容物的净重量。计算原料药的内容物的重量，表述为每一个胶囊标示量的百分含量，单个胶囊内容物净重量相对于每个胶囊的百分含量以及含量测定的结果。计算AV值。软胶囊准确称量10个完整的胶囊的单个重量并得到总重量，确保每一个胶囊与其重量对应关系不乱。然后通过适当的方法（注意使用干净和干燥的仪器如剪刀和锋利的刀片）切开胶囊，移去内容物，用适当的溶剂洗涤胶囊使其取尽。允许包藏溶剂在室温条件下从胶囊壳中蒸发出来，时间为30min，注意避免水汽的

49、吸入和损失。对单个胶囊壳进行称重，计算净含量。计算原料药的含量，表达为标示量的百分含量，药物从单个胶囊中移取出来的的净重量占每一个胶囊重量的百分含量以及含量测定结果。计算AV值。单个包装的固体制剂（包括无菌固体制剂）按照硬胶囊的过程进行操作，计算AV值。单剂量容器中的口服溶液在不超过5s时间内从10个单独的包装中倒尽内含液体，准确称量液体的总量。必要时在确定其密度的情况下计算等价的体积。计算原料药的含量，表述为标示量的百分含量，单个容器内容物的净重量占每个单位制剂液体重量的百分含量和含量测定结果。计算AV值。AV值的计算按照含量均匀度中AV值的计算方法计算AV值，除了单位剂量单个含量被单个估算的含量（下面有定义）所取代。1, 2, , n = 单个估算的供试品含量，其中i = Wi ×A /W1, W2, , Wn = 单个供试单位剂量的重量，作为重量差异A = 原料药含量（相当于标示量的%），由含量测定中的方法测定W = 单个供试品在含量测定中重量的平均值（W1, W2, , Wn）包装于玻璃或