USP905含量均勻度中英文

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. 含量均勻度建立在通過測(cè)定一定數(shù)量的單個(gè)劑量的原料藥單個(gè)含量來確定單個(gè)含量是否符合限度要求。含量均勻度測(cè)試方法可以應(yīng)用于所有的情況下。以下六種劑型要求測(cè)定含量均勻度：(C1) 包衣片，除了含有25mg或更多原料藥的薄膜包衣片，其原料藥組成占了片劑總重的25%。(C2) 經(jīng)皮系統(tǒng)(C3) 單個(gè)劑量包裝的或用僅于全身給藥（而不是局部給藥）的軟膠囊包裝的混懸劑或乳劑或凝膠劑。(C4) 包裝于單位計(jì)量進(jìn)過事先測(cè)量的過吸入劑（除了包裝于玻璃或塑料安瓿中用于噴霧的溶液劑）。對(duì)于標(biāo)簽上標(biāo)注需要使用到指定的吸入器的吸入劑和事先測(cè)量過

21、單位劑量，可參見噴霧器，鼻噴霧器，定量吸入劑和干粉吸入劑<601>。(C5) 包裝于單個(gè)劑量容器中固體（包括無菌固體），含有活性或無活性的添加劑，除了重量差異的測(cè)試中可以應(yīng)用于(W3)所列舉的特殊情況。(C6) 栓劑選擇不少于30個(gè)單位，按照劑型指定的操作進(jìn)行。當(dāng)單劑量中原料藥的量與含量測(cè)定中所要求的不同時(shí)，調(diào)整溶液稀釋的程度以及等份的體積使得最終得到溶液中含有的原料藥濃度與含量測(cè)定中的濃度在一個(gè)數(shù)量級(jí)上；再如在滴定的含量測(cè)定中，必要時(shí)使用不同濃度的滴定液以得到合適的體積。（參見滴定<541>）;也可以參見總體注意事項(xiàng)中測(cè)試法和含量測(cè)定。如果在各論中關(guān)于含量測(cè)定法有任何

22、的修改，要對(duì)計(jì)算公式和滴定因子進(jìn)行相應(yīng)的改變。當(dāng)各論中指定了特殊的含量均勻度測(cè)定法時(shí)，按下述方法對(duì)結(jié)果做任何必要的修正。1準(zhǔn)備足夠數(shù)量的劑量單位的復(fù)合樣本來提供給各論中含量測(cè)定以及各論中含量均勻度測(cè)定測(cè)試法項(xiàng)下特殊的數(shù)量要求用，這些測(cè)試法需要將片劑磨成粉末或是將單個(gè)包裝的膠囊、口服液體制劑、混懸劑、乳劑、凝膠劑或固體制劑中內(nèi)容物混合得到均一的混合物。如果不能通過上述方法得到均一的混合物，使用合適的溶劑或其它的方法來制備含有所有藥物的溶液，并使用合適的溶液等份來為指定的測(cè)試法制備供試品。2對(duì)準(zhǔn)確測(cè)量的單個(gè)包裝的膠囊、片劑、混懸劑、吸入劑或固體制劑復(fù)合樣品進(jìn)行單獨(dú)的測(cè)定，（1）按照含量測(cè)定方法；（

23、2）按照各論中含量測(cè)定測(cè)試法項(xiàng)下的方法。3通過下面兩種方法計(jì)算等量于平均單劑量的藥物的重量，（1）使用含量測(cè)定法得到的結(jié)果；（2）使用特殊測(cè)試法得到的結(jié)果。計(jì)算校正因子F公式為：F = W/PW指通過含量測(cè)試法中得到的相當(dāng)于平均單劑量的藥物重量；P 通過特殊測(cè)試法中得到的指相當(dāng)于平均單劑量的藥物重量。如果：的值大于10，使用這個(gè)校正因子是無效的。5校正因子只適用于F不小于1.030且不大于1.100的情況，或者是不小于0.900且不大于0.970的情況。如果F在0.970和1.030之間，不需要使用校正。6如果F在1.030和1.100之間，或在0.900和0.970之間，特殊測(cè)試法中得到的原

24、料藥的重量要與F相乘來計(jì)算每一個(gè)單劑量原料藥的重量。非包衣、包衣、壓膜片、膠囊、單劑量包裝的口服溶液、單劑量包裝的混懸劑、溶劑、凝膠劑（僅用于全身系統(tǒng)給藥）和單包裝的固體制劑（包括無菌固體制劑）在各論中含量測(cè)定項(xiàng)下取10個(gè)單位劑量進(jìn)行檢測(cè)，除非各論中含量均勻度測(cè)定法項(xiàng)下有另行規(guī)定。按照下述方法計(jì)算AV值。對(duì)于僅用于系統(tǒng)全身給藥的單劑量包裝中的口服液體制劑，以及單劑量包裝的混懸劑、乳劑或凝膠劑， 在進(jìn)行測(cè)定時(shí)，從單獨(dú)容器中濾干得到充分混勻的物料的含量測(cè)定不得超過5s。高粘度的產(chǎn)品在進(jìn)行含量測(cè)定時(shí)，定量的轉(zhuǎn)移單個(gè)容器中的內(nèi)容物來得到混合均勻的無聊進(jìn)行含量測(cè)定，所得到的結(jié)果為可轉(zhuǎn)移的劑量。AV的計(jì)算

25、按照下面的公式：包裝于事先定量的劑量單位的栓劑，透皮系統(tǒng)，吸入劑注意：這些劑型不需要進(jìn)行AV值的計(jì)算。對(duì)10個(gè)單位進(jìn)行單獨(dú)的含量測(cè)定，按照各論中含量測(cè)定指示的方法，除非在含量均勻度測(cè)定的測(cè)試法項(xiàng)下有另行規(guī)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.重量差異測(cè)試應(yīng)用于以下劑型：(W1) 包裝于玻璃或塑料安瓿中用于

29、噴霧吸入的溶液劑，和包裝于單位劑量容器中與軟膠囊中口服給藥溶液劑。(W2) 包裝于單個(gè)劑量容器中的固體（包括無菌固體），不含有添加劑，無論是活性的還是無活性的。(W3) 包裝于單個(gè)劑量的容器中含有或不含有添加物質(zhì)的固體（包括無菌固體），添加物質(zhì)可以具有活性也可以是無活性的。固體制劑通過真溶液和在最終容器中凍干進(jìn)行制備，并且標(biāo)簽中指定了此種制備方法。(W4) 硬膠囊，未包衣片或薄膜包衣片，含有25mg或更多的原料藥，原料藥占劑量單位重量的的25%或更多，膠囊的內(nèi)容物。其它比例更少的原料藥均勻度需要證明其符合含量均勻度要求。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. 不滿足以上重量差異測(cè)試要求的所有劑型需要進(jìn)行含量均勻度測(cè)試。當(dāng)需要符合含量均勻度測(cè)試要求時(shí)，可以應(yīng)用總體注意事項(xiàng)中替代方法的使用要求。在最終劑型單位的原料藥濃度相對(duì)標(biāo)準(zhǔn)偏差不超過2%的情況下，生產(chǎn)商可以應(yīng)用重量差異測(cè)試保證符合含量均勻度測(cè)試要求。RSD的測(cè)定可以根據(jù)生產(chǎn)商的過程驗(yàn)證和藥物開發(fā)數(shù)據(jù)來確定。在每劑量單位濃度

47、等于以按照重量劃分的每劑量單位含量測(cè)定結(jié)果時(shí)，濃度RSD指的是每個(gè)劑量單位（w/w, 或w/v）的濃度的RSD。參見表2中RSD公式。當(dāng)重量差異測(cè)試按照這種方法使用時(shí)，如果進(jìn)行含量均勻度測(cè)試，產(chǎn)品必須符合官方藥典中含量均勻度測(cè)試的要求。選擇不少于30個(gè)劑量單位，按照下列指定的劑型進(jìn)行測(cè)定。按照各論中指示得到的含量測(cè)定的結(jié)果被指定為結(jié)果A，表述為標(biāo)示量的百分含量（參見AV值的計(jì)算）。假定濃度（每劑量單位的原料藥的重量）是均一的。非包衣或薄膜包衣片劑準(zhǔn)確逐一稱量10片片劑的重量。計(jì)算原料藥的含量，表述為每一個(gè)片劑標(biāo)示量或每一片單獨(dú)片劑重量的百分含量以及含量測(cè)定的結(jié)果。計(jì)算AV值。硬膠囊準(zhǔn)確稱量10

48、個(gè)膠囊的單個(gè)重量，確保每一個(gè)膠囊與其重量的對(duì)應(yīng)關(guān)系。使用適當(dāng)?shù)姆椒ㄒ迫∶恳粋€(gè)膠囊的內(nèi)容物。準(zhǔn)確稱量每一個(gè)膠囊空殼，通過從各自的總重量減去膠囊空殼的重量計(jì)算每一個(gè)膠囊的內(nèi)容物的凈重量。計(jì)算原料藥的內(nèi)容物的重量，表述為每一個(gè)膠囊標(biāo)示量的百分含量，單個(gè)膠囊內(nèi)容物凈重量相對(duì)于每個(gè)膠囊的百分含量以及含量測(cè)定的結(jié)果。計(jì)算AV值。軟膠囊準(zhǔn)確稱量10個(gè)完整的膠囊的單個(gè)重量并得到總重量，確保每一個(gè)膠囊與其重量對(duì)應(yīng)關(guān)系不亂。然后通過適當(dāng)?shù)姆椒ǎㄗ⒁馐褂酶蓛艉透稍锏膬x器如剪刀和鋒利的刀片）切開膠囊，移去內(nèi)容物，用適當(dāng)?shù)娜軇┫礈炷z囊使其取盡。允許包藏溶劑在室溫條件下從膠囊殼中蒸發(fā)出來，時(shí)間為30min，注意避免水汽的

49、吸入和損失。對(duì)單個(gè)膠囊殼進(jìn)行稱重，計(jì)算凈含量。計(jì)算原料藥的含量，表達(dá)為標(biāo)示量的百分含量，藥物從單個(gè)膠囊中移取出來的的凈重量占每一個(gè)膠囊重量的百分含量以及含量測(cè)定結(jié)果。計(jì)算AV值。單個(gè)包裝的固體制劑（包括無菌固體制劑）按照硬膠囊的過程進(jìn)行操作，計(jì)算AV值。單劑量容器中的口服溶液在不超過5s時(shí)間內(nèi)從10個(gè)單獨(dú)的包裝中倒盡內(nèi)含液體，準(zhǔn)確稱量液體的總量。必要時(shí)在確定其密度的情況下計(jì)算等價(jià)的體積。計(jì)算原料藥的含量，表述為標(biāo)示量的百分含量，單個(gè)容器內(nèi)容物的凈重量占每個(gè)單位制劑液體重量的百分含量和含量測(cè)定結(jié)果。計(jì)算AV值。AV值的計(jì)算按照含量均勻度中AV值的計(jì)算方法計(jì)算AV值，除了單位劑量單個(gè)含量被單個(gè)估算的含量（下面有定義）所取代。1, 2, , n = 單個(gè)估算的供試品含量，其中i = Wi ×A /W1, W2, , Wn = 單個(gè)供試單位劑量的重量，作為重量差異A = 原料藥含量（相當(dāng)于標(biāo)示量的%），由含量測(cè)定中的方法測(cè)定W = 單個(gè)供試品在含量測(cè)定中重量的平均值（W1, W2, , Wn）包裝于玻璃或