溶出度檢查法美國(guó)藥典

1、精選優(yōu)質(zhì)文檔-傾情為你奉上<711> DISSOLUTION溶出度(USP39-NF34 Page 540)General chapter is being harmonized with the corresponding texts of the European Pharmacopoeia and/or the Japanese Pharmacopoeia. These pharmacopeias have undertaken to not make any unilateral change to this harmonized c

2、hapter.通則<711>溶出度與歐盟藥典和日本藥典中的相應(yīng)部分相統(tǒng)一。這三部藥典承諾不做單方面的修改。Portions of the present general chapter text that are national USP text, and therefore not part of the harmonized text, are marked with symbols to specify this fact.本章中的部分文字為本國(guó)USP內(nèi)容，并沒(méi)有與其他藥典統(tǒng)一。此部分以（   ）標(biāo)注。This test i

3、s provided to determine compliance with the dissolution requirements  where stated in the individual monograph  for dosage forms administered orally. In this general chapter, a dosage unit is defined as 1 tablet or 1 capsule or the amount specified.  Of the types of app

4、aratus designs described herein, use the one specified in the individual monograph. Where the label states that an article is enteric coated and a dissolution or disintegration test does not specifically state that it is to be applied to delayed-release articles and is included in the indi

5、vidual monograph, the procedure and interpretation given for Delayed-Release Dosage Forms are applied, unless otherwise specified in the individual monograph.本測(cè)試用于檢測(cè)藥品口服制劑的溶出度是否符合各論中的規(guī)定。本章中，除另有規(guī)定外，單位制劑定義為1片或1粒膠囊。對(duì)于本章中所述多種儀器，使用各論中規(guī)定的種類。除各論中另有規(guī)定外，如果檢品是腸溶衣片且各論中的溶出度或崩解時(shí)限檢查項(xiàng)下沒(méi)有特別指出適用遲釋劑的，使用本章中適

6、用于遲釋劑的流程和解釋。 FOR DOSAGE FORMS CONTAINING OR COATED WITH GELATIN涂有或包含明膠的劑型If the dosage form containing gelatin does not meet the criteria in the appropriate Acceptance Table (see Interpretation, Immediate-Release Dosage Forms, Extended-Release Dosage Forms, or Dela

7、yed-Release Dosage Forms) because of evidence of the presence of cross-linking, the dissolution procedure should be repeated with the addition of enzymes to the medium, as described below, and the dissolution results should be evaluated starting at the first stage of the appropriate Acceptance

8、Table. It is not necessary to continue testing through the last stage (up to 24 units) when criteria are not met during the first stage testing, and evidence of cross-linking is observed.如果劑型中含有明膠，其不符合驗(yàn)收表中的標(biāo)準(zhǔn)（見(jiàn)判斷，速釋制劑，延釋制劑，緩釋制劑），因?yàn)榇嬖诿髂z交聯(lián)結(jié)合作用，它的溶解過(guò)程與外加的媒介酶是重復(fù)的，見(jiàn)下面的描述，并且溶解結(jié)果可以通過(guò)適當(dāng)?shù)尿?yàn)收表的開(kāi)始的第一階段標(biāo)準(zhǔn)進(jìn)行評(píng)估。如果

9、溶出結(jié)果不滿足第一階段的測(cè)試標(biāo)準(zhǔn)，那么就沒(méi)有必要繼續(xù)測(cè)試到最后階段，并且也證明了明膠交聯(lián)結(jié)合作用的存在。Gelatin, in the presence of certain compounds and/or in certain storage conditions, including but not restricted to high humidity and temperature, may present cross-linking. A pellicle may form on the external and/or internal surface of the gelatin

10、 capsule shell or on the dosage form that prevents the drug from being released during dissolution testing (see more information in ).明膠，存在于某一處方和/或某一儲(chǔ)存條件下，如：高溫高濕，可能存在明膠交聯(lián)結(jié)合作用。在膠囊殼或其他劑型的外表面和/或內(nèi)表面形成一層膜阻止溶出試驗(yàn)過(guò)程中藥物的釋放（見(jiàn)膠囊-溶出度檢測(cè)和相關(guān)質(zhì)量屬性<1094> ）。Note  All references to a chapter a

11、bove <1000> are for information purposes only, for use as a helpful resource. These chapters are not mandatory unless explicitly called out for this application.注-超過(guò)<1000>章節(jié)的所有引用應(yīng)用的目的僅為提供參考信息。這些章節(jié)是非強(qiáng)制的，除非另有規(guī)定。Dissolution Medium with pH 4.0 pH 4.0的溶出介質(zhì)Enzyme: Peps

12、in, activity determined by the procedure in , in the Reagent Specifications section 酶：胃蛋白酶，活性視試劑規(guī)格部分中的胃蛋白酶提純過(guò)程而定。Amount: A quantity of pepsin that results in an activity of NMT 750,000 Units/L of dissolution medium數(shù)量：一些胃蛋白酶對(duì)溶出介質(zhì)提供NMT 750,000 單位/L的生物活性。Dissolution Medium with

13、 pH >4.0 and <6.8 pH >4.0 和 <6.8的溶出介質(zhì)Enzyme: Papain, activity determined by the Assay test in the monograph for  or bromelain, activity determined by the procedure in, in the Reagent Specifications section 酶：木瓜蛋白酶，活性視木瓜蛋白酶專論中的分析測(cè)試而定；或菠蘿蛋白酶，活性視試劑規(guī)格部分中的菠蘿

14、蛋白酶生產(chǎn)過(guò)程而定。Amount: A quantity of papain that results in an activity of NMT 550,000 Units/L of dissolution medium, or a quantity of bromelain that results in an activity of NMT 30 gelatin-digesting units (GDU)/L of dissolution medium數(shù)量：一些木瓜蛋白酶對(duì)溶出介質(zhì)提供NMT 550,000 單位/L的生物活性；一些菠蘿蛋白酶對(duì)溶出介質(zhì)提供NMT 30明膠消化單

15、位/L的生物活性。Dissolution Medium with pH 6.8 pH 6.8的溶出介質(zhì)Enzyme: Pancreatin, protease activity determined by the procedure in Assay for protease activity (Casein digestive power) in the monograph for  酶：胰液素，蛋白酶活性視胰液素專論中的蛋白酶活性（酪蛋白消化能力）分析中的生產(chǎn)過(guò)程而定。Amount: A quantity of

16、 pancreatin that results in a protease activity of NMT 2000 Units/L of dissolution medium數(shù)量：一些胰液素對(duì)溶出介質(zhì)提供NMT 550,000 單位/L的蛋白酶活性。Dissolution Medium Containing Surfactant or Other Ingredients Known to Denature the Enzyme含有表面活性劑或其他已知成分變性酶的溶出介質(zhì)If the dissolution medium contains surfactant or other ingred

17、ients that are known to denature the enzyme used, a pretreatment step in the dissolution testing of the dosage form may be applied. This pretreatment step is done using the specified dissolution medium without the surfactant or the ingredient and with the addition of the appropriate amount of enzyme

18、 according to the medium pH. The amount of enzyme added is appropriate to the volume of dissolution medium used in the pretreatment. To achieve the specified medium volume for the final dissolution testing, the pretreatment step may be conducted with a smaller volume of medium without the ingredient

19、 such that the final volume is obtained when the ingredient is added at the end of the pretreatment step. All of the other conditions of the test (apparatus, rotation, or flow rate) should remain as described in the method or monograph. Typically, the duration of the pretreatment step is NMT 15 min.

20、 The required pretreatment time should be evaluated on a case-by-case basis and should be scientifically justified. This time should be included in the total time of the test. As an example, if the total time of the test is 45 min and 15 min are used in the pretreatment step, the test will continue

21、for 30 min after the addition of the ingredient.  如果溶出介質(zhì)中添加了表面活性劑或其他已知成分的變性酶，那么此溶出實(shí)驗(yàn)就要把預(yù)處理步驟考慮進(jìn)去。預(yù)處理過(guò)程就是是根據(jù)溶出介質(zhì)的pH來(lái)確定加入酶的量，此處的溶出介質(zhì)不含有表面活性劑和原料。酶加入的量要適合預(yù)處理所用的溶出介質(zhì)的體積。為了達(dá)到最終溶出試驗(yàn)所需要的特定的溶出介質(zhì)的體積，預(yù)處理階段所用的溶出介質(zhì)（不含原料）的體積要稍微小點(diǎn)，如此在預(yù)處理最后階段加入原料的時(shí)候方可獲得最終的溶出介質(zhì)體積。其他所有的測(cè)試條件（如：設(shè)備、轉(zhuǎn)速、流速）應(yīng)該與方法或?qū)Ｕ撝忻枋龅囊恢隆ＭǔｎA(yù)處理階段

22、的持續(xù)時(shí)間為NMT 15 min。所需的預(yù)處理時(shí)間應(yīng)該根據(jù)具體案例具體分析，且應(yīng)該科學(xué)、合理。預(yù)處理時(shí)間應(yīng)該包含在實(shí)驗(yàn)的總時(shí)間里。例如，如果實(shí)驗(yàn)的總時(shí)間為45min，預(yù)處理時(shí)間為15min，那么加入原料后實(shí)驗(yàn)還要繼續(xù)進(jìn)行30min。USP Reference Standards 11  USP Prednisone Tablets RS. USP參考標(biāo)準(zhǔn)<11>-USP強(qiáng)的松片 RS。APPARATUS儀器Apparatus 1 (Basket Apparatus) 第1法（籃法）The assembly consists of the fo

23、llowing: a vessel, which may be covered, and made of glass or other inert, transparent material; a motor; a metallic drive shaft; and a cylindrical basket. The vessel is partially immersed in a suitable water bath of any convenient size or heated by a suitable device, such as a heating jacket.

24、The water bath or heating device permits holding the temperature inside the vessel at 37 ± 0.5° during the test and keeps the bath fluid in constant, smooth motion. No part of the assembly, including the environment in which the assembly is placed, contributes significant motion, agitation

25、, or vibration beyond that due to the smoothly rotating, stirring element. An apparatus that permits observation of the specimen and of the stirring element during the test is preferable. The vessel is cylindrical, with a hemispherical bottom and  with one of the following dimensions and c

26、apacities: for a nominal  capacity of 1 L, the height is 160210 mm, and its inside diameter is 98106 mm;  for a nominal capacity of 2 L, the height is 280300 mm, and its inside diameter is 98106 mm; and for a nominal capacity of 4 L, the height is 280300 mm, and its inside diamet

27、er is 145155 mm  . Its sides are flanged at the top. A fitted cover may be used to retard evaporation. The shaft is positioned so that its axis is NMT 2 mm at any point from the vertical axis of the vessel and rotates smoothly and without significant wobble that could affect the resul

28、ts. A speed-regulating device is used that allows the shaft rotation speed to be selected and maintained at the specified rate  given in the individual monograph  within ±4%.設(shè)備由下列部分組成：有蓋或無(wú)蓋的溶出杯，由玻璃或其他惰性的透明材料1制成；馬達(dá)；轉(zhuǎn)軸；轉(zhuǎn)籃。溶出杯部分浸沒(méi)在合適大小的水浴中，或者由合適的裝置加熱，例如電熱套。水浴或加熱裝置需能在測(cè)試過(guò)程中將杯內(nèi)溫度保

29、持在37±0.5，并且容許杯內(nèi)液體持續(xù)、平緩的流動(dòng)。整個(gè)儀器包括周圍的環(huán)境，除了平穩(wěn)轉(zhuǎn)動(dòng)的攪拌部件，不得有明顯的運(yùn)動(dòng)，攪動(dòng)或振動(dòng)。儀器最好能允許在檢測(cè)過(guò)程中能夠觀察到檢品和攪拌部件。溶出杯為圓柱形，底部為半球形，尺寸和容積如下：名義容積1L的，高160-210mm，內(nèi)徑98-106mm；名義容積2L的，高280-300mm，內(nèi)徑98-106mm；名義容積4L的，高280-300mm，內(nèi)徑145-155mm。內(nèi)壁頂部有緣。可以使用合適的蓋子減緩溶劑蒸發(fā)2。轉(zhuǎn)軸與溶出杯的縱軸在任意部位不得相差差過(guò)2mm，轉(zhuǎn)動(dòng)平滑，無(wú)明顯搖晃以至于影響檢測(cè)結(jié)果。速度調(diào)節(jié)裝置控制轉(zhuǎn)軸的轉(zhuǎn)速，并可維持在各論中

30、規(guī)定值的±4%范圍內(nèi)。Shaft and basket components of the stirring element are fabricated of stainless steel, type 316, or other inert material, to the specifications shown in . A basket having a gold coating of about 0.0001 inch (2.5 µm) thick may be used. A dosage unit is placed in a dry basket

31、 at the beginning of each test. The distance between the inside bottom of the vessel and the bottom of the basket is maintained at 25 ± 2 mm during the test.轉(zhuǎn)軸和籃筐組件由316號(hào)不銹鋼或者其他惰性材料制成，尺寸如圖1所示。可使用鍍金厚度0.0001英寸（2.5m）的籃筐。開(kāi)始檢測(cè)時(shí)，將一劑藥品至于干燥的籃筐中。在測(cè)試過(guò)程中，溶出杯底部到籃筐底部的距離應(yīng)保持在25±2mm。Figure 1. Basket stirri

32、ng element.圖1. 轉(zhuǎn)籃組成Apparatus 2 (Paddle Apparatus) 第2法（槳法）Use the assembly from Apparatus 1, except that a paddle formed from a blade and a shaft is used as the stirring element. The shaft is positioned so that its axis is NMT 2 mm from the vertical axis of the vessel at any point and rotates sm

33、oothly without significant wobble that could affect the results. The vertical center line of the blade passes through the axis of the shaft so that the bottom of the blade is flush with the bottom of the shaft. The paddle conforms to the specifications shown in . The distance of 25 ± 2 mm

34、between the bottom of the blade and the inside bottom of the vessel is maintained during the test. The metallic or suitably inert, rigid blade and shaft compose a single entity. A suitable two-part, detachable design may be used, provided that the assembly remains firmly engaged during the test. The

35、 paddle blade and shaft may be coated with a suitable coating so as to make both of them inert. The dosage unit is allowed to sink to the bottom of the vessel before rotation of the blade is started. A small, loose piece of nonreactive material, such as NMT a few turns of wire helix, may be attached

36、 to dosage units that would otherwise float. An alternative sinker device is shown in . Other validated sinker devices may be used.使用第1法中的設(shè)備，除了使用一個(gè)由葉片和轉(zhuǎn)軸組成的槳作為攪拌單元。轉(zhuǎn)軸與溶出杯的縱軸在任意部位不得相差差過(guò)2mm，轉(zhuǎn)動(dòng)平滑，無(wú)明顯搖晃以至于影響檢測(cè)結(jié)果。葉片的垂直中性線穿過(guò)轉(zhuǎn)軸的軸線，葉片的下緣與轉(zhuǎn)軸底部平齊。槳的尺寸應(yīng)符合圖2中的規(guī)定。在測(cè)試過(guò)程中，葉片底部與溶出杯底部的距離應(yīng)保持在25±2mm。金屬或硬質(zhì)的葉片

37、和轉(zhuǎn)軸應(yīng)是一個(gè)整體。兩部分組合的設(shè)計(jì)也可以使用，只要組件在檢測(cè)過(guò)程中牢固固定在一起?？梢栽跇~和轉(zhuǎn)軸上涂布合適的涂層以使其為惰性。在槳葉開(kāi)始旋轉(zhuǎn)前，將一劑藥品沉至溶出杯底。如果藥劑浮在頁(yè)面上，可以在其上附著一個(gè)惰性，松弛的小部件，例如幾圈線圈，使其沉沒(méi)。圖2是一種可替代使用的沉子。其他經(jīng)驗(yàn)證的沉子也可以使用。Figure 2. Paddle stirring element.圖2. 攪拌槳組成Figure 2a. Alternative sinker. All dimensions are expressed in mm.圖2a. 可選的沉降籃（單位均為mm）Apparatus 3 (Reci

38、procating Cylinder) 第3法（往復(fù)圓筒法）not accepted by the japanese pharmacopoeia日本藥典未收錄The assembly consists of a set of cylindrical, flat-bottomed glass vessels; a set of glass reciprocating cylinders; inert fittings (stainless steel type 316 or other suitable material), and screens that are made of suitab

39、le nonsorbing and nonreactive material and that are designed to fit the tops and bottoms of the reciprocating cylinders; and a motor and drive assembly to reciprocate the cylinders vertically inside the vessels; if desired, index the reciprocating cylinders horizontally to a different row of vessels

40、. The vessels are partially immersed in a suitable water bath of any convenient size that permits holding the temperature at 37 ± 0.5° during the test. No part of the assembly, including the environment in which the assembly is placed, contributes significant motion, agitation, or vibratio

41、n beyond that due to the smooth, vertically reciprocating cylinder. A device is used that allows the reciprocation rate to be selected and maintained at the specified dip rate  given in the individual monograph  within ±5%. An apparatus that permits observation of the specim

42、ens and reciprocating cylinders is preferable. The vessels are provided with evaporation caps that remain in place for the duration of the test. The components conform to the dimensions shown in , unless otherwise specified  in the individual monograph  .所用設(shè)備包含一套圓柱形平底玻璃杯；一套玻

43、璃往復(fù)圓筒；惰性配件（316號(hào)不銹鋼或其他合適的材質(zhì)）；由合適的非吸附，不反應(yīng)材料制成的篩網(wǎng)，擋在往復(fù)圓筒的上下兩端；一套馬達(dá)和傳動(dòng)裝置，將圓筒在玻璃杯中垂直往復(fù)運(yùn)動(dòng)，如果需要，也可以將往復(fù)圓筒平行移至另一行玻璃杯中。玻璃杯部分浸沒(méi)在合適尺寸的水浴中，水浴溫度保持在37±0.5。儀器的任何部件，以及儀器所處的環(huán)境，都不應(yīng)當(dāng)引起明顯的移動(dòng)，攪動(dòng)，振動(dòng)，除了平滑的垂直往復(fù)運(yùn)動(dòng)的圓筒。使用設(shè)備維持往復(fù)速度在各論中所規(guī)定值的±5%范圍內(nèi)。儀器最好可以在檢測(cè)過(guò)程中觀察到樣品和往復(fù)圓筒。玻璃杯配有蒸發(fā)帽，在檢測(cè)中一直蓋在玻璃杯上。除另有規(guī)定外，各部分的尺寸如圖3所示。Figure 3.

44、 Apparatus 3 (reciprocating cylinder).圖3. 圖3 第3法（往復(fù)圓筒法）設(shè)備Apparatus 4 (Flow-Through Cell) 第4法（流通池法）The assembly consists of a reservoir and a pump for the Dissolution medium; a flow-through cell; and a water bath that maintains theDissolution medium at 37 ± 0.5°. Use the specified

45、 cell size  as given in the individual monograph  .所用設(shè)備包含一個(gè)溶出介質(zhì)的容器和相應(yīng)的泵，一個(gè)流通池和水浴。水浴將溶出介質(zhì)保持在37±0.5。使用各論中規(guī)定的尺寸。The pump forces the Dissolution medium upward through the flow-through cell. The pump has a delivery range between 240 and 960 mL/h, with standard flow rate

46、s of 4, 8, and 16 mL/min. It must deliver a constant flow (±5% of the nominal flow rate); the flow profile is sinusoidal with a pulsation of 120 ± 10 pulses/min. A pump without pulsation may also be used. Dissolution test procedures using a flow-through cell must be characterized with resp

47、ect to rate and any pulsation.泵將溶出介質(zhì)推動(dòng)，向上通過(guò)流通池。泵的傳輸能力在240到960mL每小時(shí)之間，標(biāo)準(zhǔn)速率為4，8，16mL每分鐘。泵的流速必須均勻（名義流量的±5%以內(nèi)）。泵的流量特性曲線應(yīng)為正弦波，脈沖為每分鐘120 ± 10 沖。無(wú)脈沖泵也可以使用。使用流通池法的溶出度測(cè)試必須對(duì)應(yīng)特定的流速和脈沖。The flow-through cell (see  and ), of transparent and inert material, is mounted vertically with a fil

48、ter system (specified in the individual monograph) that prevents escape of undissolved particles from the top of the cell; standard cell diameters are 12 and 22.6 mm; the bottom cone is usually filled with small glass beads of about 1-mm diameter with one bead of about 5 mm, positioned at the apex t

49、o protect the fluid entry tube; and a tablet holder (see  and ) is available for positioning of special dosage forms, e.g., inlay tablets. The cell is immersed in a water bath, and the temperature is maintained at 37 ± 0.5°.由透明且惰性材料制成的流通池（見(jiàn)圖4和圖5）垂直安放，配有過(guò)濾系統(tǒng)（在各論中規(guī)定）以防止未溶解的顆粒從

50、流通池頂部逸出。標(biāo)準(zhǔn)的流通池直徑為12和22.6mm。底部的錐形通常填有直徑約1mm的小玻璃珠，其中一顆約5mm大的玻璃珠置于頂點(diǎn)處，以保護(hù)液體輸入管。流通池配有藥片架（見(jiàn)圖4和圖5）一滿足特殊制劑的需要，如泡騰片。流通池浸沒(méi)在37±0.5的水浴中。專心-專注-專業(yè)Figure 4. Apparatus 4: large cell for tablets and capsules (top); tablet holder for the large cell (bottom). (All measurements are expressed in mm unless noted ot

51、herwise.)圖4. 第4法設(shè)備，盛裝片劑和膠囊的大流通池（上），大藥片架（下）。（除另有說(shuō)明，所有尺寸單位為mm。）Figure 5. Apparatus 4: small cell for tablets and capsules (top); tablet holder for the small cell (bottom). (All measurements are expressed in mm unless noted otherwise.)圖5 第4法設(shè)備，盛裝片劑和膠囊的小流通池（上），小藥片架（下）。（除另有說(shuō)明，所有尺寸單位為mm。）The apparatus use

52、s a clamp mechanism and two O-rings to assemble the cell. The pump is separated from the dissolution unit to shield the latter against any vibrations originating from the pump. The position of the pump should not be on a level higher than the reservoir flasks. Tube connections are as short as possib

53、le. Use suitably inert tubing, such as polytef, with about a 1.6-mm inner diameter and chemically inert, flanged-end connections.流通池使用一個(gè)架子和2個(gè)O形圈固定。泵與溶出單元分開(kāi)，以防止泵的振動(dòng)干擾到后者。泵的水平位置不得高于溶出介質(zhì)容器。管線連接盡可能短。使用合適的惰性管線，如聚四氟乙烯，內(nèi)徑1.6mm。法蘭連接也應(yīng)為化學(xué)惰性。apparatus suitability設(shè)備適用性The determination of suitability of a test

54、 assembly to perform dissolution testing must include conformance to the dimensions and tolerances of the apparatus as given above. In addition, critical test parameters that have to be monitored periodically during use include volume and temperature of the Dissolution medium, rotation speed (A

55、pparatus 1 and Apparatus 2), dip rate (Apparatus 3), and flow rate of medium (Apparatus 4).溶出度測(cè)試儀器的適用性必須包括與上述各儀器在尺寸和限度上的一致性。另外，必須在使用過(guò)程中定期觀測(cè)的關(guān)鍵測(cè)試參數(shù)包括：溶出介質(zhì)的溫度和體積，轉(zhuǎn)速（第1法和第2法），浸沒(méi)頻率（第3法）和溶出介質(zhì)流速（第4法）。Determine the acceptable performance of the dissolution test assembly periodically.  T

56、he suitability for the individual apparatus is demonstrated by the Performance verification test.定期檢測(cè)溶出度測(cè)試設(shè)備的性能。單個(gè)設(shè)備的適用性由性能驗(yàn)證測(cè)試給出。Performance verification test, Apparatus 1 and Apparatus 2: Test USP Prednisone Tablets RS according to the operating conditions specified. The appara

57、tus is suitable if the results obtained are within the acceptable range stated in the technical data sheet specific to the lot used and the apparatus tested.性能驗(yàn)證測(cè)試，第1法和第2法：根據(jù)規(guī)定的操作條件測(cè)試USP強(qiáng)的松片RS。如果結(jié)果在技術(shù)數(shù)據(jù)表上該批次和所用儀器的的可接受范圍內(nèi)，則設(shè)備是適用的。Performance verification test, Apparatus 3: To come.性能驗(yàn)證測(cè)試，第3法待續(xù)Pe

58、rformance verification test, Apparatus 4: To come. 性能驗(yàn)證測(cè)試，第4法待續(xù) PROCEDURE測(cè)試方法Apparatus 1 and Apparatus 2第1法和第2法immediate-release dosage forms速釋制劑Place the stated volume of the Dissolution medium (±1%) in the vessel of the specified apparatus  given in the individua

59、l monograph  , assemble the apparatus, equilibrate the Dissolution medium to 37 ± 0.5°, and remove the thermometer. Place 1 dosage unit in the apparatus, taking care to exclude air bubbles from the surface of the dosage unit, and immediately operate the apparatus at the

60、 specified rate  given in the individual monograph  . Within the time interval specified, or at each of the times stated, withdraw a specimen from a zone midway between the surface of the Dissolution medium and the top of the rotating basket or blade, NLT 1 cm from the

61、vessel wall. Note  Where multiple sampling times are specified, replace the aliquots withdrawn for analysis with equal volumes of fresh Dissolution medium at 37° or, where it can be shown that replacement of the medium is not necessary, correct for the volume change in

62、the calculation. Keep the vessel covered for the duration of the test, and verify the temperature of the mixture under test at suitable times.  Perform the analysis  as directed in the individual monograph  using a suitable assay method. Repeat the test with additional dosage form units.將各論中給出的溶出介質(zhì)量（±1%）加入到規(guī)定的容器中，組裝好設(shè)備，平衡溶出介質(zhì)溫度在37±0.5，移出溫度計(jì)。將1單位劑量的藥品小心加入設(shè)備中，注意避免表面產(chǎn)生氣泡。立即按照各