EP7.0 欧洲药典 2.9.38. Particle-size distribution 粒度分布_中文_翻译

PARTICLE-SIZE DISTRIBUTION ESTIMATION BY ANALYTICAL SIEVING(17)

筛分是对粉末和颗粒通过颗粒大小分布进行分级的最老的方法之一。当使用织物筛布时，筛分基本上依据筛网的中间尺寸大小（即幅度或宽度）对颗粒进行分类。如果大部分的颗粒大于75微米左右，采用机筛法是最合适的。对于更小的颗粒，由于质量轻，在筛分过程中，它们不能克服表面凝聚力和粘附力，使颗粒相互粘在一起或粘在筛网上，从而导致那些本该能通过筛孔的颗粒而未能通过。对于这样的材料，其它的振动方式，如喷气筛分或声波筛分器筛分可能更为合适。然而，筛分有时可被用于一些中值颗粒尺寸小于75微米的粉末或颗粒，只要该方法经过验证。在制药行业，对单一粉末或颗粒进行粗略等级分类时，筛分通常是被选择的方法。这是一个尤其引人注目的方法，因为该方法仅依据粒径大小对粉末和颗粒进行颗粒大小分级，在大多数情况下，干粉状态下即可进行检测。

Sieving is one of the oldest methods of classifying powders and granules by particle-size distribution. When using a woven sieve cloth, the sieving will essentially sort the particles by their intermediate size dimension (i.e. breadth or width). Mechanical sieving is most suitable where the majority of the particles are larger than about 75 µm. For smaller particles, their light weight provides insufficient force during sieving to overcome the surface forces of cohesion and adhesion that cause the particles to stick to each other and to the sieve, and thus cause particles that would be expected to pass through the sieve to be retained. For such materials other means of agitation such as air-jet sieving or sonic-sifter sieving may be more appropriate. Nevertheless, sieving can sometimes be used for some powders or granules having median particle sizes smaller than 75 µm where the method can be validated. In pharmaceutical terms, sieving is usually the method of choice for classification of the coarser grades of single powders or granules. It is a particularly attractive method in that powders and granules are classified only on the basis of particle size, and in most cases the analysis can be carried out in the dry state.

筛分方法的局限性包括：需要可观质量的样品（通常至少为25克，这取决于粉末或颗粒的密度和试验筛的直径）；以及在筛分那些容易堵塞筛孔的油性或有粘着力的粉末或颗粒时存在困难。该方法在本质上是一个对颗粒大小的两个维度的估计，因为是否能通过筛孔，通常更多地取决于最大宽度和厚度，而非长度。 Among the limitations of the sieving method are the need for an appreciable amount of sample (normally at least 25 g, depending on the density of the powder or granule, and the diameter of the test sieves) and the difficulty in sieving oily or other cohesive powders or granules that tend to clog the sieve openings. The method is essentially a two-dimensional estimate of size because passage through the sieve aperture is frequently more dependent on maximum width and thickness than on length.

此方法拟用于某个单一物质的总体粒度大小分布的估计。而不用于测定通过或保留在1个或2个筛上颗粒的比例。

This method is intended for estimation of the total particle-size distribution of a

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single material. It is not intended for determination of the proportion of particles passing or retained on 1 or 2 sieves.

按照干筛法中所述对颗粒度大小分布进行估计，除非个论中另有规定。可能遇到的困难是在过筛临近终点时（如材料不容易通过筛子），或当需要使用筛分范围（小于75µm）中偏细的筛子时，使用替代粒度分级方法时必须慎重。

Estimate the particle-size distribution as described under Dry sieving method, unless otherwise specified in the individual monograph. Where difficulty is experienced in reaching the endpoint (i.e. material does not readily pass through the sieves) or when it is necessary to use the finer end of the sieving range (below 75 µm), serious consideration must be given to the use of an alternative particle-sizing method.

筛分必须在不会造成测试样增加或失去水分的条件下进行。筛分环境中的相对湿度必须加以控制，以防止样品吸收水分或水分流失。在缺乏相反证据的情况下，进行筛分分析测试通常是在周围环境湿度中进行。适用于某个特殊材料的任何特殊条件必须在个论中详细描述。

Sieving is carried out under conditions that do not cause the test sample to gain or lose moisture. The relative humidity of the environment in which the sieving is carried out must be controlled to prevent moisture uptake or loss by the sample. In the absence of evidence to the contrary, analytical test sieving is normally carried out at ambient humidity. Any special conditions that apply to a particular material must be detailed in the individual monograph.

过筛检测原则。检测用试验筛：一个经过简单编织能够织成类似方孔的金属丝网，再连接到一个开口筒状容器的底部所构成。基本的检测方法包括：将筛子按照筛孔粗细程度从小到大的顺序逐一堆叠起来，然后将待测试的粉末置于顶层筛面上。套筛经受一个标准时间的摇动，然后每层筛上留有的待测试粉末的质量就可以准确确定。这个测试方法可得出粉末在每个筛子孔径范围内的质量百分比。 Principles of analytical sieving. Analytical test sieves are constructed from a woven-wire mesh, which is of simple weave that is assumed to give nearly square apertures and is joined to the base of an open cylindrical container. The basic analytical method involves stacking the sieves on top of one another in ascending degrees of coarseness, and then placing the test powder on the top sieve. The nest of sieves is subjected to a standardised period of agitation, and then the mass of material retained on each sieve is accurately determined. The test gives the mass percentage of powder in each sieve size range.

这种对单一的药物粉末进行颗粒尺寸分布估计的筛分过程通常用于至少有80％的颗粒大于75µm的粉末。使用分析过筛法测定颗粒大小分布过程中涉及的尺寸参数是指颗粒可通过的最小方孔的边长。

This sieving process for estimating the particle-size distribution of a single pharmaceutical powder is generally intended for use where at least 80 per cent of the particles are larger than 75 µm. The size parameter involved in determining particle-size distribution by analytical sieving is the length of the side of the minimum

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square aperture through which the particle will pass.

试验筛 TEST SIEVES

适合药典测试的试验筛应符合ISO3310-1：试验筛-技术要求和检测- 第1部分：金属丝编织网试验筛（见表2.9.38.-1）现行版的要求。除非个论中另有规定，应使用表2.9.38.-1中列出的ISO筛主要尺寸，在个别地区推荐使用这些尺寸。 Test sieves suitable for pharmacopoeial tests conform to the current edition of ISO 3310-1: Test sieves-Technical requirements and testing - Part 1: Test sieves of metal wire cloth (see Table 2.9.38.-1). Unless otherwise specified in the monograph, use those ISO sieves listed as principal sizes in Table 2.9.38.-1 that are recommended in the particular region.

表 2.9.38.-1 Table 2.9.38.-1. ISO标示孔径 ISO Nominal Aperture 美国筛子编号 US Sieve No. 推荐的USP筛子（µm） Recommended USP Sieves(µm) 欧洲筛子编号 European Sieve No. 日本筛子编号 Japanese Sieve No. 主要尺寸补充尺寸Principal Supplementary sizes sizes R 20/3 R 20 R 40/3 11.20mm 11.20mm 11.20mm 10.00mm 9.50mm 9.00mm 8.00mm 8.00mm 8.00mm 7.10mm 6.70mm 6.30mm 5.60mm 5.60mm 5.60mm 5.00mm 4.75mm 4.50mm 4.00mm 4.00mm 4.00mm 3.55mm 3.35mm 3.15mm 2.80mm 2.80mm 2.80mm 2.50mm 2.36mm 2.24mm 2.00mm 2.00mm 2.00mm 1.80mm 1.70mm 1.60mm 1.40mm 1.40mm 1.40mm 5 6 7 8 10 12 14 3 / 9

4000 2800 2000 1400 11 200 5600 4000 2800 2000 1400 3.5 4 4.7 5.5 6.5 7.5 8.6 10 12 16 14 18 1000 1000 16 20 18 25 710 710 22 30 26 35 500 500 30 40 36 45 355 355 42 50 60 250 250 60 70 70 80 180 180 83 100 100 120 125 125 119 140 140 170 90 90 166 200 200 230 63 63 235 270 282 325 45 45 330 38 391 筛子选择时，应能涵盖测试样品中存在的所有颗粒大小的尺寸范围。建议套筛各

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1.00mm 710µm 500µm 355µm 250µm 180µm 125µm 90µm 63µm 45µm 1.25mm 1.12mm 1.00mm 900µm 800µm 710µm 630µm 560µm 500µm 450µm 400µm 355µm 315µm 280µm 250µm 224µm 200µm 180µm 160µm 140µm 125µm 112µm 100µm 90µm 80µm 71µm 63µm 56µm 50µm 45µm 40µm 1.18mm 1.00mm 850µm 710µm 600µm 500µm 425µm 355µm 300µm 250µm 212µm 180µm 150µm 125µm 106µm 90µm 75µm 63µm 53µm 45µm 38µm 个筛网的筛孔面积按递增。套筛最上面安装最粗的筛网，底部安装最细的筛

网。以微米或毫米表示试验筛筛孔大小。

Sieves are selected to cover the entire range of particle sizes present in the test sample. A nest of sieves having a

progression of the area of the sieve openings is

recommended. The nest of sieves is assembled with the coarsest screen at the top and the finest at the bottom. Use micrometres or millimetres in denoting test sieve openings.

试验筛由不锈钢或其次情况下由黄铜或其它合适的非反应性金属丝制成。 Test sieves are made from stainless steel or, less preferably, from brass or another suitable non-reactive wire.

试验筛的校准和再校准应根据ISO3310-1现行版规定。在使用前应仔细检查筛网是否有严重变形和破裂，尤其是在网框接合处。可采用光学方法对筛网进行调校来估计筛孔的平均尺寸，以及筛孔开口目数的变化。或者，可采用尺寸范围212-850µm的标准玻璃球对筛孔开口进行有效性评估。除非在个论中另有规定，筛分检测必须在受控的室温和周围环境中的相对湿度条件下进行。

Calibration and recalibration of test sieves is in accordance with the current edition of ISO 3310-1. Sieves are carefully examined for gross distortions and fractures, especially at their screen frame joints, before use. Sieves may be calibrated optically to estimate the average opening size, and opening variability, of the sieve mesh. Alternatively, for the evaluation of the effective opening of test sieves in the size range of 212-850 µm, standard glass spheres are available. Unless otherwise

specified in the individual monograph, perform the sieve analysis at controlled room temperature and at ambient relative humidity.

试验筛的清洁。理想的情况下，只能使用低压喷气或液体流对试验筛进行清洗。如果某些筛孔被测试粉末颗粒堵住了，万不得已的条件下，可小心轻轻擦拭。 Cleaning test sieves. Ideally, test sieves are cleaned using only a low-pressure air jet or a liquid stream. If some apertures remain blocked by test particles, careful gentle brushing may be used as a last resort.

测试样/供试品. 如果在药典个论中没有给出某个具体材料所需供试样品的质量，对于直径200mm的试验筛，可使用25-100克的测试样品，具体量取决于该材料的堆积密度。对于直径76mm的筛子，所能容纳的测试样品质量大约是直径200mm试验筛所能容纳样品质量的1/7。通过精密称取不用质量的样品，如25克、50克和100克在同一机械振动筛上振动同样的时间来确定最适当的用于筛分检测的测试样质量，（注:如果25克样品和50克样品的检测结果是相似的，但100克样品通过最细的筛子时却呈现出一个较低的比例，那100克的样品量就太多了）。如果只有10-25克可用样品，可用符合相同质量标准的金属丝网但直径更小的试验筛，但必须重新确定筛分终点。可能会需要使用更小质量的试验样品(如低至5g)。对于具有较低表观颗粒密度的检品，或者大部分是由直径高度接近

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的颗粒所构成的检品，200毫米的筛子可能需要5克以下样品，以避免筛孔过度阻塞。在具体筛分分析方法的验证过程中，最好考虑到并解决好筛孔阻塞问题。 Test sample. If the test sample mass is not given in the monograph for a particular material, use a test sample having a mass of 25-100 g, depending on the bulk density of the material, for test sieves having a 200 mm diameter. For 76 mm sieves, the amount of material that can be accommodated is approximately 1/7 that which can be accommodated by a 200 mm sieve. Determine the most appropriate mass for a given material by test sieving accurately weighed samples of different masses, such as 25 g, 50 g and 100 g, for the same time period on a mechanical shaker (note: if the test results are similar for the 25 g and 50 g samples, but the 100 g sample shows a lower percentage through the finest sieve, the 100 g sample size is too large). Where only a sample of 10-25 g is available, smaller diameter test sieves conforming to the same mesh specifications may be substituted, but the endpoint must be

redetermined. The use of test samples having a smaller mass (e.g. down to 5 g) may be needed. For materials with low apparent particle density, or for materials mainly comprising particles with a highly iso-diametrical shape, sample masses below 5 g for a 200 mm screen may be necessary to avoid excessive blocking of the sieve. During validation of a particular sieve-analysis method, it is expected that the problem of sieve blocking will have been addressed.

如果测试样品受不同湿度影响而易于吸收或损失较多量的水分，则检测必须在适当受控的环境中进行。同样的，如果知道测试样品是产生静电的，必须仔细观察确保这样的静电不至于影响筛分检测。可能需要添加0.5％(m/m)的抗静电剂，如胶体二氧化硅和/或氧化铝，以减少这种影响。如果上述两个影响不能被消除的话，必须选择替代的粒度检测技术。

If the test material is prone to absorbing or losing significant amounts of water with varying humidity, the test must be carried out in an appropriately controlled environment. Similarly, if the test material is known to develop an electrostatic charge, careful observation must be made to ensure that such charging does not influence the analysis. An antistatic agent, such as colloidal silicon dioxide and/or aluminum oxide, may be added at a 0.5 per cent (m/m) level to minimise this effect. If both of the above effects cannot be eliminated, an alternative particle-sizing technique must be selected.

振动方法。市场上可以买到几种不同的筛子和粉末振动装置，所有这些都可能被用于筛分检测。然而，不同的振动方法，可能得到不同的筛分结果以及不同的筛分终点判定，因为检测过程中是不同类型、不同量级的力作用到每个受测颗粒上。可以使用机械振动或电磁振动，要么是垂直振荡要么是水平圆周运动，要么是轻拍要么是轻拍加水平圆周运动。还可使用气流夹带颗粒。结果中必须标明所使用的振动方法和振动参数（如果是变量的话），因为振动条件的变化将给出不同的筛分检测结果及不同的筛分终点，而且在某些情况下足以导致失败/不符合要求的检测结果。

Agitation methods. Several different sieve and powder-agitation devices are

commercially available, all of which may be used to perform sieve analyses. However,

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the different methods of agitation may give different results for sieve analyses and endpoint determinations because of the different types and magnitudes of the forces acting on the individual particles under test. Methods using mechanical agitation or electromagnetic agitation, and that can induce either a vertical oscillation or a horizontal circular motion, or tapping or a combination of both tapping and

horizontal circular motion are available. Entrainment of the particles in an air stream may also be used. The results must indicate which agitation method was used and the agitation parameters used (if they can be varied), since changes in the agitation conditions will give different results for the sieve analysis and endpoint

determination, and may be sufficiently different to give a failing result under some circumstances.

筛分终点的判定。当任一试验筛上留下的样品质量与原先质量相比，质量变化不再超过5%或0.1克时（76mm直径的筛子是10％），就表明筛分可以结束了。如果在某个指定筛子上样品量低于样品总量的5％，那么此次筛分的结束时间点可增加至样品质量变化不超过该筛上原先质量的20％。

Endpoint determination. The test sieving analysis is complete when the mass on any of the test sieves does not change by more than 5 per cent or 0.1 g (10 per cent in the case of 76 mm sieves) of the previous mass on that sieve. If less than 5 per cent of the total sample mass is present on a given sieve, the endpoint for that sieve is increased to a mass change of not more than 20 per cent of the previous mass on that sieve.

如果筛分结束时发现在任何一个筛子上留有的样品质量超过样品总量的50％，除非在各论中特别规定，否则应重新检测，而且要在套筛中留有过多质量的筛子与下一个筛孔最粗的筛子之间增加筛孔更粗的中间尺寸筛网，比如增加套筛中漏掉的ISO系列筛网。

If more than 50 per cent of the total sample mass is found on any one sieve, unless this is indicated in the monograph, the test is repeated, but with the addition to the sieve nest of a more coarse sieve intermediate between that carrying the excessive mass and the next coarsest sieve in the original nest, i.e. addition of the ISO series sieve omitted from the nest of sieves.

筛分方法 SIEVING METHODS 机械振动（干筛法）。将每个试验筛的皮重四舍五入至0.1g。将精确称取的供试样品置于最高层（筛孔最粗）的筛网，合上盖子。振动套筛5分钟，然后从套筛中小心取出每个筛子，且不得有材料损失。重新称量每个筛子，得出每个筛上剩余的样品质量。用同样的方式得出收集盘中的样品质量。重新组装套筛，振动5分钟。按照前面所述移除并称量每个筛子。重复这些步骤，直至符合筛分结束条件（见试验筛下筛分终点判定）。分析完成后进行物料平衡计算。损失总量不得超过原始测试样品质量的5％。

Mechanical agitation (Dry sieving method). Tare each test sieve to the nearest 0.1 g. Place an accurately weighed quantity of test sample on the top (coarsest) sieve, and replace the lid. Agitate the nest of sieves for 5 min, then carefully remove each sieve

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from the nest without loss of material. Reweigh each sieve, and determine the mass of material on each one. Determine the mass of material in the collecting pan in a similar manner. Re-assemble the nest of sieves, and agitate for 5 min. Remove and weigh each sieve as previously described. Repeat these steps until the endpoint criteria are met (see Endpoint determination under Test sieves). Upon completion of the analysis, reconcile the masses of material. Total loss must not exceed 5 per cent of the mass of the original test sample.

用另一新的样品重新进行检测，但使用单筛的筛分时间为上面所用时间之和。确保该筛分时间符合筛分终点判定要求。在对某个具体材料进行筛分结束时间确认后，倘若粒度分布处于正常的变化范围内，则某个固定的使用单筛的筛分时间可用于今后的检测。

Repeat the analysis with a fresh sample, but using a single sieving time equal to that of the combined times used above. Confirm that this sieving time conforms to the requirements for endpoint determination. When this endpoint has been validated for a specific material, then a single fixed time of sieving may be used for future analyses, providing the particle-size distribution falls within normal variation.

如果有证据表明，在任一筛上保留下来的是聚合体而非单颗粒，则使用机械干粉筛分法将不可能得到良好的重现性，而且必须要使用不同的粒度分析法。 If there is evidence that the particles retained on any sieve are aggregates rather than single particles, the use of mechanical dry sieving is unlikely to give good reproducibility, and a different particle-size analysis method must be used.

气体夹带法（喷气筛分和声波筛分）

Air-entrainment methods (Air-jet and sonic-sifter sieving). 市场上有不同种类的使用气流的设备可用于筛分。一次使用单个筛子的系统被称为喷气筛分。它使用与干筛法项下描述相同的筛分方法，只是用一个标准化的气流喷射代替了正常的振动装置。它需要在单个筛子上进行连续分析，从最细的筛子开始，以得到粒度分布。喷气筛分法通常要使用较细的试验筛，而不是普通干筛法中的试验筛。这种技术更适于尺寸过大或过小的材料。

Different types of commercial equipment that use a moving air current are available for sieving. A system that uses a single sieve at a time is referred to as air-jet sieving. It uses the same general sieving methodology as that described under Dry sieving method, but with a standardised air jet replacing the normal agitation mechanism. It requires sequential analyses on individual sieves starting with the finest sieve to obtain a particle-size distribution. Air-jet sieving often includes the use of finer test sieves than used in ordinary dry sieving. This technique is more suitable where only oversize or undersize fractions are needed.

在声波筛分法中，使用到套筛，而且样品从一个垂直振荡空气筒中带入，这个垂直振荡的空气筒以每分钟设定脉冲数的频率把测试样品提升起来，然后又带回至网眼空隙中。当使用声速过筛时，可能有必要把样品量降至5g。

In the sonic-sifter method, a nest of sieves is used, and the test sample is carried in a

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vertically oscillating column of air that lifts the sample and then carries it back against the mesh openings at a given number of pulses per minute. It may be necessary to lower the sample amount to 5 g when sonic sifting is employed.

当机械筛分技术无法提供有意义的分析时，喷气筛分和声波筛分法可能对于粉体或颗粒是非常有用的。

The air-jet sieving and sonic-sifter sieving methods may be useful for powders or granules when the mechanical sieving techniques are incapable of giving a meaningful analysis.

这些方法高度依赖气流中粉末的分散情况。如果是处在筛分范围下限（即小于75微米），此要求可能很难达到，因为这种条件下颗粒更易于聚合，尤其是当这些料粉还具有产生静电的倾向的话。基于上述理由，筛分终点的判定尤其关键，确认超粒径料由单个粒子组成而不是由聚合物组成，这也是非常重要的。 These methods are highly dependent upon proper dispersion of the powder in the air current. This requirement may be hard to achieve if the method is used at the lower end of the sieving range (i.e. below 75 µm), when the particles tend to be more cohesive, and especially if there is any tendency for the material to develop an electrostatic charge. For the above reasons endpoint determination is particularly critical, and it is very important to confirm that the oversize material comprises single particles and is not composed of aggregates.

阐释INTERPRETATION

除了在每个单筛和收集器内留有的样品质量，原始数据必须包括试验样品的质量、筛分总时间、精确的筛分方法学，以及任何可变参数的设定值。

The raw data must include the mass of the test sample, the total sieving time, the precise sieving methodology, and the set values for any variable parameters, in addition to the masses retained on the individual sieves and in the pan.

原始数据可以很方便地转换成累积质量分布图，如果要求以小粒径累积质量的方式展示分布的话，所用筛子的范围必须包括所有颗粒都能通过的那个筛子。如果有证据表明，任何一个试验筛上保留的材料是在筛分过程中形成的单个粒子的聚合物，则此次筛分检测将是无效的。

It may be convenient to convert the raw data into a cumulative mass distribution, and if it is desired to express the distribution in terms of a cumulative mass undersize, the range of sieves used must include a sieve through which all the material passes. If there is evidence on any of the test sieves that the material remaining on it is composed of aggregates formed during the sieving process, the analysis is invalid.

翻译： LLeo Nov 2013

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