2.9.38. PARTICLE-SIZE DISTRIBUTION ESTIMATION BY ...

1 EUROPEAN PHARMACOPOEIA PARTICLE-SIZE DISTRIBUTION ESTIMATION by analytical sieving01/2008 PARTICLE-SIZEDISTRIBUTION ESTIMATION BYANALYTICAL SIEVINGS ieving is one of the oldest methods of classifying powdersand granules by PARTICLE-SIZE DISTRIBUTION . When usinga woven sieve cloth, the sieving will essentially sort theparticles by their intermediatesize dimension ( , breadthor width). Mechanical sieving is most suitable where themajority of the particles are larger than about 75 m. Forsmaller particles, their light weight provides insufficient forceduring sieving to overcome the surface forces of cohesionand adhesion that cause the particles to stick to each otherand to the sieve, and thus cause particles that would beexpected to pass through the sieve to be retained.

2 For suchmaterials other means of agitation such as air-jet sieving orsonic sifting may be more appropriate. Nevertheless, sievingcan sometimes be used for some powders or granules havingmedian particle sizes smaller than 75 m where the methodcan be validated. In pharmaceutical terms, sieving is usuallythe method of choice for classification of the coarser gradesof single powders or granules. It is a particularly attractivemethod in that powders and granules are classified only onthe basis of particle size, and in most cases the analysis canbe carried out in the dry the limitations of the sieving method are the needfor an appreciable amount of sample (normally at least 25 g,depending on the density of the powder or granule, and thediameter of the test sieves) and difficulty in sieving oily orother cohesive powders or granules that tend to clog thesieve openings.

3 The method is essentially a two-dimensionalestimate of size because passage through the sieve apertureis frequently more dependent on maximum width method is intended for ESTIMATION of the totalparticle-size DISTRIBUTION of a single material. It is notintended for determination of the proportion of particlespassing or retained on 1 or 2 the PARTICLE-SIZE DISTRIBUTION as described under Drysieving method, unless otherwise specified in the individualmonograph. Where difficulty is experienced in reaching theendpoint ( , material does not readily pass through thesieves) or when it is necessary to use the finer end of thesieving range (below 75 m), serious consideration must begiven to the use of an alternative particle-sizing is carried out under conditions that do not cause thetest sample to gain or lose moisture.

4 The relative humidity ofthe environment in which the sieving is carried out must becontrolled to prevent moisture uptake or loss by the the absence of evidence to the contrary, analytical testsieving is normally carried out at ambient humidity. Anyspecial conditions that apply to a particular material must bedetailed in the individual of analytical from a woven-wire mesh, which is of simpleweave that is assumed to give nearly square apertures andis sealed into the base of an open cylindrical container.

5 Thebasic analytical method involves stacking the sieves on topof one another in ascending degrees of coarseness, and thenplacing the test powder on the top sieve. The nest of sievesis subjected to a standardised period of agitation, and thenthe weight of material retained on each sieve is accuratelydetermined. The test gives the weight percentage of powderin each sieve size sieving process for estimating the particle-sizedistribution of a single pharmaceutical powder is generallyintended for use where at least 80 per cent of the particlesare larger than 75 m.

6 The size parameter involved indetermining PARTICLE-SIZE DISTRIBUTION by analytical sievingis the length of the side of the minimum square aperturethrough which the particle will SIEVESTest sieves suitable for pharmacopoeial tests conform to themost current edition ofISO 3310-1: Test sieves Technicalrequirements and testing - Part 1: Test sieves of metal wirecloth(see Table ). Unless otherwise specified in themonograph, use those ISO sieves listed as principal sizesin Table that are recommended in the Nominal AperturePrinci-pal Sieves(mesh) R20 R40 mm mm mm11 mm mm mm mm mm mm mm mm mm mm mm mm mm mm mm mm mm mm mm mm 181000100016900 mGeneralNotices(1)

7 PARTICLE-SIZE distributionestimation by analytical sievingEUROPEAN PHARMACOPOEIA Nominal AperturePrinci-pal Sieves(mesh) 20/3 R 20 R 40/3850 m2018800 m710 m 710 m 710 m 2571071022630 m600 m 3026560 m500 m 500 m 500 m 3550050030450 m425 m4036400 m355 m 355 m 355 m 4535535542315 m300 m5050280 m250 m 250 m 250 m6025025060224 m212 m7070200 m180 m 180 m 180 m8018018083160 m150 m 100100140 m125 m 125 m 125 m 120125125119112 m106 m 140140100 m90 m 90 m 90 m170909016680 m75 m20020071 m63 m 63 m 63 m 230636323556 m53 m27028250 m45

8 M 45 m 45 m 325454533040 m38 m38391 Sieves are selected to cover the entire range of particlesizes present in the test sample. A nest of sieves havingaprogression of the area of the sieve openings isrecommended. The nest of sieves is assembled with thecoarsest screen at the top and the finest at the micrometres or millimetres in denoting test sieveopenings (Note: mesh numbers are provided in the table forconversion purposes only).Test sieves are made from stainless steel or, less preferably,from brass or other suitable non-reactive and recalibration of test sieves is in accordancewith the most current edition of ISO 3310-1.

9 Sieves arecarefully examined for gross distortions and fractures,especially at their screen frame joints, before use. Sieves maybe 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 sievesin the size range of 212-850 m, standard glass spheresare available. Unless otherwise specified in the individualmonograph, perform the sieve analysis at controlled roomtemperature and at ambient relative test sieves.

10 Ideally, test sieves are cleaned usingonly a low-pressure air jet or a liquid stream. If someapertures remain blocked by test particles, careful gentlebrushing may be used as a last sample. If the test sample mass is not given in themonograph for a particular material, use a test samplehaving a mass between 25-100 g, depending on the bulkdensity of the material, for test sieves having a 200 mmdiameter. For 76 mm sieves, the amount of material thatcan be accommodated is approximately 1/7 that whichcan be accommodated by a 200 mm sieve.