á786ñPARTICLE SIZE DISTRIBUTION ESTIMATION BY ANALYTICAL SIEVING
Sieving is one of the oldest methods of classifying powders by particle size distribution.Sieving is most suitable where the majority of the particles are larger than about 75µm,although it can be used for some powders having smaller particle sizes 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.It is a particularly attractive method in that powders are classified only on the basis of particle size,and in most cases the analysis can be carried out in the dry state.
Among the limitations of the sieving method are the need for an appreciable amount of sample (normally at least 25g)and difficulty in sieving oily or other cohesive powders 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.
This method is intended for estimation of the total particle size distribution of a single material.It is not intended for determination of the proportion of particles passing or retained on one or two sieves.
Estimate the particle size distribution as described under Method I,unless otherwise specified in the individual monograph.Method Iis the dry sieving method.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 75µm),Method II,which is a wet sieving technique,may be used;however,in the latter case serious consideration should be given to the use of an alternative particle-sizing method.
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 sealed into 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 standardized period of agitation,and then the weight of material retained on each sieve is accurately determined.The test gives the weight percentage of powder in each sieve size range.
This sieving process for estimating the particle size distribution of a single pharmaceutical powder is generally intended for use where at least 80%of the particles are larger than 75µm.The size parameter involved in determining particle size distribution by analytical sieving is the length of the side of the minimum square aperture through which the particle will pass.
Test sieves suitable for pharmacopeial tests conform to the most current edition of International Organization for Standardization Specification ISO3310-1:Test sievesTechnical requirements and Testing1(see Table 1).Unless otherwise specified in the monograph,use those ISOsieves listed as principal sizes in Table 1.
Table 1.Sizes of Standard Sieve Series in Range of Interest2
Sieves are selected to cover the entire range of particle sizes present in the test specimen.This nest of sieves is completed by a well-fitting collecting pan at its base and lid at its top.Use micrometers or millimeters in denoting test sieve openings.[NOTEMesh numbers are provided in the table for conversion purposes only.]Test sieves are made from stainless steel or,less preferably,from brass or other suitable nonreactive wire.
Calibration and recalibration of test sieves is in accordance with the most current edition of ISO3310-1.Sieves should be 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 212to 850µm,Standard Glass Spheres are available from the National Institute of Standards and Technology as Standard Reference Material 1018.Unless otherwise specified in the individual monograph,perform the sieve analysis at controlled room temperature and a relative humidity between 20%and 70%.
Cleaning Test Sieves Ideally,test sieves should be cleaned using only an air jet or a liquid stream.If some apertures remain blocked by test particles,careful gentle brushing may be used as a last resort.Washing sieves in hot water is not recommended since the sieves can distort and rupture during heating and cooling.If it is necessary to use water,it should be used at ambient temperature and the sieve dried by first using a volatile water-miscible solvent to remove the water and then a low-pressure air jet to remove the solvent.This procedure should be carried out in a fume hood or cabinet that conforms to local regulations.
Test Specimen If the test specimen weight is not given in the monograph for a particular material,use a test specimen having a weight between 25and 100g,depending on the bulk density of the material,and test sieves having a 200-mm diameter.Determine the most appropriate weight for a given material by test sieving accurately weighed specimens of different weights,such as 25,50,and 100g,for the same time period on a mechanical shaker.[NOTEIf the test results are similar for the 25-g and 50-g specimens,but the 100-g specimen shows a lower percentage through the finest sieve,the 100-g specimen size is too large.]Where only a specimen of 10to 25g is available,smaller diameter test sieves conforming to the same ISOmesh specifications may be substituted,but the endpoint must be redetermined.
If the test material is prone to picking up 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 is not influencing the analysis.If both of the above effects cannot be eliminated,an alternative particle-sizing technique must be selected.
Agitation Methods Use a mechanical device that imparts either a rotating-tap (200to 300horizontal revolutions and 140to 300taps per minute)or vibratory (1to 2mm amplitude)motion to the sieves as the reference method of agitating test sieves,unless otherwise stated in the individual monograph.Methods utilizing entrainment of the particles in an air stream may also be used.The results must indicate the type of sieving method used.
Endpoint Determination The test sieving analysis is complete when the weight on any of the test sieves does not change by more than 5%(10%in the case of 76-mm sieves)of the previous weight on that sieve.If less than 5%of the total specimen weight is present on a given sieve,the endpoint for that sieve is increased to a weight change of not more than 20%of the previous weight on that sieve.
If more than 50%of the total specimen weight is found on any one sieve,the test should be repeated,but with the addition to the sieve nest of the next coarsest sieve to that carrying the excessive weight,i.e.,addition of the ISOseries sieve omitted from the USPseries in Table 1.For example,if more than 50%of the total specimen weight is found on the 180-µm sieve,the ISO212-µm sieve should be placed between the 180-µm and 250-µm sieves in the sieve nest.
Method I(Dry Sieving Method) Tare each test sieve to the nearest 0.1g.Place an accurately weighed quantity of test specimen on the top (coarsest)sieve,and replace the lid.Agitate the nest of sieves for 5minutes.Then carefully remove each from the nest without loss of material.Reweigh each sieve,and determine the weight of material on each sieve.Determine the weight of material in the collecting pan in a similar manner.Reassemble the nest of sieves,and agitate for 5minutes.Remove and weigh each sieve as previously described.Repeat these steps until the endpoint criteria are met (see Endpoint Determinationunder Test Sieves).Upon completion of the analysis,reconcile the weights of material.Total losses must not exceed 5%of the weight of the original test specimen.
Repeat the analysis with a fresh specimen,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 does not change significantly.
If there is evidence that the particles retained on any sieve are aggregates rather than single particles,the use of dry sieving is unlikely to give good reproducibility,and Method IIshould be considered as one preferred technique.
Method II(Wet Sieving Method) Modify the lid and collecting pan of the sieve nest to permit addition of a liquid onto the surface of the top sieve and collection of the liquid from the pan.Dry a sufficient quantity of the test material to constant weight at a temperature that will not have a detrimental effect on the material,e.g.,if it is a solvate.Select a liquid in which the test specimen is insoluble,and modify the sieving method as indicated below.Thoroughly disperse the dried test material in the liquid by gentle agitation,and pour this dispersion onto the top sieve.Rinse the dispersion equipment with fresh liquid,and add the rinsings to the top sieve.Feed the sieving liquid through a suitable pumping mechanism to the nozzle(s)in the lid,and collect the sieving liquid from the pan in a suitable container.Continue the wet sieving process until the emerging liquid appears free of particles.
Remove each sieve from the sieve nest,and dry each sieve to constant weight at the same temperature as that used above.Determine the weight of dried material on each sieve.
Air Jet and Sonic Sifter Sieving Different types of commercial equipment that use a moving air current are available for sieving.Asystem that uses a single sieve at a time is referred to as air jetsieving.It uses the same general sieving methodology as that described under Method I,but with a standardized air jet replacing the normal agitation mechanism.It requires sequential analyses on individual sieves to provide a particle size distribution.This technique is more suitable where only oversize or undersize fractions are needed.
In the sonic siftingmethod,a nest of sieves is used,and the test specimen is carried in a vertically oscillating column of air that lifts the specimen and then carries it back against the mesh openings at a given number of pulses per minute.The air jet sieving and sonic sieving methods may be useful when the standard dry and wet sieving techniques are incapable of giving a meaningful analysis.
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 75µm),when the particles tend to be more cohesive,and especially if there is any tendency for the material to develop an electrostatic charge.In the latter case an antistatic agent,such as silicon dioxide or aluminum oxide,may be added at the 0.5%(w/w)level to minimize this effect.For the above reasons endpoint determination is particularly critical,and it is very important to confirm that the oversize material is in fact single particles and is not composed of aggregates.
The raw data must include the weight of test specimen,the total sieving time,and the precise sieving methodology,in addition to the weights on the individual sieves and in the pan.It may be convenient to convert the raw data into a cumulative weight distribution,and if it is desired to express the distribution in terms of a cumulative weight undersize,the range of sieves used should 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.
1 ISO3310-1:2000(E)analytical sieve specifications are identical to those of the appropriate nominal aperture in ASTM E11-01US Standard Sieve Series.