786 PARTICLE SIZE DISTRIBUTION ESTIMATION BY ANALYTICAL SIEVING
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, the 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 sifting 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.
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 test sieves) and 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.
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 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 should be given to the use of an alternative particle-sizing method.
Sieving should be 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 should 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 should be detailed in the individual monograph.
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 75 µm. 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 ISO 3310-1: Test SievesTechnical Requirements and Testing (see Table 1). Unless otherwise specified in the monograph, use those ISO sieves listed as principal sizes in Table 1. Unless otherwise specified in the monograph, use those ISO sieves listed in Table 1 as recommended in the particular region.
Table 1. Sizes of Standard Sieve Series in Range of Interest
Sieves are selected to cover the entire range of particle sizes present in the test specimen. A nest of sieves having a 2 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 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 ISO 3310-1. 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 212 to 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.
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.
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 25 and 100 g, depending on the bulk density of the material, and test sieves having a 200-mm diameter. For 76-mm sieves, the amount of material that can be accommodated is approximately 1/7th that which can be accommodated on a 200-mm sieve. Determine the most appropriate weight for a given material by test sieving accurately weighed specimens of different weights, such as 25, 50, and 100 g, 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 10 to 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 isodiametrical shape, specimen weights 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.
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. An antistatic agent, such as colloidal silicon dioxide and/or aluminum oxide, may be added at a 0.5 percent (m/m) level to minimize this effect. If both of the above effects cannot be eliminated, an alternative particle-sizing technique must be selected.
Agitation Methods Several different sieve and powder agitation devices are commercially available, all of which may be used to perform sieve analyses. However, the different methods of agitation may give different results for sieve analyses and endpoint determinations because of the different types and magnitude 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), because changes in the agitation conditions will give different results for the sieve analysis and endpoint determinations, and may be sufficiently different to give a failing result under some circumstances.
Endpoint Determination The test sieving analysis is complete when the weight on any of the test sieves does not change by more than 5% or 0.1 g (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, unless this is indicated in the monograph, the test should be repeated, but with the addition to the sieve nest of a more coarse sieve, intermediate between that carrying the excessive weight and the next coarsest sieve in the original nest, i.e., addition of the ISO series sieve omitted from the nest of sieves.
Dry Sieving Method Tare each test sieve to the nearest 0.1 g. Place an accurately weighed quantity of test specimen on the top (coarsest) sieve, and replace the lid. Agitate the nest of sieves for 5 minutes. 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 5 minutes. 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 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 falls within normal variation.
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 should be used.
Air Entrainment Methods
Air Jet and Sonic Sifter Sieving 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 the Dry Sieving Method, but with a standardized 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 those used in ordinary dry sieving. This technique is more suitable where only oversize or undersize fractions are needed.
In the sonic sifting method, 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. It may be necessary to lower the sample amount to 5 g, when sonic sifting is employed.
The air jet sieving and sonic sieving methods may be useful for powders or granules when mechanical 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 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.
The raw data must include the weight of test specimen, the total sieving time, and the precise sieving methodology and the set values for any variable parameters, in addition to the weights retained 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.