PRACTICAL 4 : SIEVING

Title  : Sieving

Date : 17 November 2014

Objective 
To determine the lactose and Microcrystalline cellulose ( MCC ) particle size distribution  by using sieve nest.

Introduction
 

                A sieve, or sifter, is a device for separating wanted elements from unwanted material or for characterizing the particle size distribution of a sample. In its most common form it consists of a woven wire screen, with square apertures, rigidly mounted in a shallow cylindrical metal frame. For coarse sieving a perforated plate screen with square or round holes may be used in place of wire mesh. Square hole perforated plate sieves range down to 4mm and round hole sieves down to 1mm aperture. In this practical we are given a common excipient used in tablet formulation which is lactose.We are required to used the sieve nest to determine the particle size and the size distribution of lactose.

     

               Nevertheless, ‘micro’ sieving can be carried out down to 5 microns using special techniques. Particle size, as measured by test sieving, may be specified simply by quoting two sieve sizes, one through which the particles have passed, and the other on which they are retained. However, the most frequent use of test sieving is for measuring the size spread, i.e., the particle size distribution. Test sieving is not the only method available for particle size analysis, but it is certainly the most widely used and probably the most important. The materials which are tested in this experiment are lactose and microcrystalline cellulose.

Apparatus
 
1.sieve metal

2.weighing scale

Material 

Lactose

 

Microcrystalline cellulose ( MCC )

Experimental Procedure

1. 100g of lactose was weighed

2. A 'sieve nest' was prepared in ascending order and assigned appropriate sieve size

3. The lactose powder was put into the sieve.

4. Then, lactose powder was sieved for 20 minutes.

5. The results obtained was recorded and a histogram on powder particle size distribution was built.

6. The process was repeated with MCC.



Result

                                 



Microcrystalline Cellulose ( MCC ) Particle Size     Distribution

         



                      Lactose Particle Size Distribution            

             


Questions

1. What are the average particle size foe both lactose and MCC ?

 The overall particle size for both lactose and MCC is between 53 µm  and 150 µm.

2. What other methods can you use to determine the size of particle ?

      (a)Microscopy

       There are two types of microscopy which are optical microscopy (1-150µm) and electron

microscopy (0.001µ-). Microscopy is being considered as an absolute measurement of particle

size because it able to examine each particle individually. It can distinguish aggregates from

single particles. When coupled to image analysis computers each field can be examined, and a

distribution obtained.

     (b)  Sedimentation techniques

This method depends on the fact that the terminal velocity of a particle in a fluid increases with size. The particle size distribution of fine powder can be determined by examining a sedimenting  suspension of the powder.

    (c)  Electrical sensing zone method – Coulter Counter

Instrument measures particle volume which can be expressed as dv : the diameter of a sphere

that has the same volume as the particle. The number and size of particles suspended in an

electrolyte is determined by causing them to pass through an orifice an either side of which is

immersed an electrode. The changes in electric impedance (resistance) as particles pass through

the orifice generate voltage pulses whose amplitude are proportional to the volumes of the

particles.

  (d)  Optical sensing zone method

  (e)  Laser light scattering techniques

For laser diffraction, particles pass through a laser beam and the light scattered by them is

collected over a range of angles in the forward direction. The angles of diffraction are, in the

simplest case inversely related to the particle size.The particles pass through an expanded and

collimated laser beam in front of a lens in whose focal plane is positioned a photosensitive detector

consisting of a series of concentric rings.Distribution of scattered intensity is analysed by

computer to yield the particle size distribution. For Photon Correlation Spectroscopy, the rate of

change of these light fluctuations is used to determine the size distribution of the particles

scattering light.

3. What are the importance of particle size in a pharmaceutical formulation?

For solid or suspension delivery systems, bioavailability is often directly related to particle size because it controls dissolution/solubility characteristics. Dissolution rate is directly proportional to particle surface area (Noyes-Whitney equation), so a finer particle size promotes faster drug dissolution. Particle size distribution is also relevant as a narrow distribution produces more uniform dissolution. Formulations with even a small number of relatively large particles may take some time to dissolve completely, but this may be the design intent.For suspensions, stability is an important issue because if the active ingredient settles there is a greater chance of non-uniform delivery. Stokes' law relates settling velocity to the physical characteristics of the fluid and the size of particles in the suspension. The relationship here is a strong one: velocity correlates with the square of particle diameter. For suspension stability, a very low settling velocity is preferable and is more easily achieved with finer particles. Perhaps less obviously, particle size may also affect a formulation's behaviour during processing and, ultimately, its content uniformity, which is critical.

Discussion

                   In this experiment, lactose and microcrystalline cellulose (MCC) were being observed for their particle size distribution. The method used was sieving method. It is also known as sieve analysis. Sieve analysis involves a nested column of sieves with wire mesh cloth (screen). See the separate Mesh (scale) page for details of sieve sizing. The sieve that has larger apertures was placed on top of the ones that having smaller apertures. This means, the sieve that have diameter of aperture of 425 µm will be placed at the top followed by 300 µm, 200 µm, 150 µm, and 53 µm. The column is typically placed in a mechanical shaker. The shaker shakes the column, usually for some fixed amount of time. After the shaking is complete the material on each sieve is weighed. The weight of the sample of each sieve is then divided by the total weight to give a percentage retained on each sieve.

                  From this experiment it shows that most particles size of lactose are in the range of 53 - 150µm (63.13 %) followed by range of 150 – 200µm (30.79 %) and 53 µm ( 3.65 %)respectively. While as for MCC, most particles size are in the range of 53 – 150 µm( 88.41 %) followed by less than 53 µm (6.50 %) and a range of 150 – 200µm (3.45 %).

                 For the particles cannot pass a certain sieve, it is because the particles are bigger than the aperture of the sieve. By this, we can deduce that most particles of MCC were finer than those of lactose.

                  At the end of the experiment, lactose and MCC in each sieve were collected back and were weighed. The final total weight of the lactose ( 98.17 g ) and MCC ( 99.55 g ) was not equal to the initial sample weight of 100g. The particles might loss to the environment ( by air movement/ wind ) during handling of the samples. During transferring of the samples from place to place we also not managed to cover the sample completely. Furthermore, the finer particles are prone to adhere or attach to the sieve nest. Some particles will also be escape from the sieving machine when the machine is operating. Thus, we have to make sure the sieving column was closed properly with the lid and clamped tightly to prevent the particles escaped from the sieving machine. We also need to make sure the sieving nest is clean and dry before conducting the experiment to obtain accurate results. However, the weight loss is very minute and negligible.

Conclusion

Most particles size of lactose are in the range of 53 - 150µm (63.13 %) followed by range of 150 – 200µm (30.79 %) and 53 µm ( 3.65 %)respectively. While as for MCC, most particles size are in the range of 53 - 150µm( 88.41 %) followed by less than 53 µm (6.50 %) and a range of 150 – 200µm (3.45 %). The overall particle size of MCC is smaller than lactose.

References

Jillavenkatesa A, Dapkunas S J, Lin-Sien Lum, Particle Size Characterization, NIST Special Publication , 2001


Martin,A.N, Physical Pharmacy: Physical Chemistry Principles in Pharmaceutical Sciences. 5th Edition. Philadelphia: Lea & Febiger, 2006


Paul Kippax, Particle size analysis, Pharmaceutical Technology Europe, 2009 from http://www.pharmtech.com/pharmtech/Analytical/Particle-size-analysis/ArticleStandard/Article/detail/588633

From http://www.horiba.com/scientific/products/particle-characterization/applications/pharmaceuticals/