Sieving

Objectives

• To determine particle size distribution of powder and the size of solid particle of  lactose and microcrystalline cellulose (MCC) by sieve nest.
• To determine the size of particles.  

Date of Experiment

19 November 2015

Introduction

Sieves are commonly used to break down agglomerates, and determine the size and size distribution of a particular powder. A sieve nest as diagram below is used to determine the particle size and the size distribution of the powders.

Apparatus And Materials

Lactose, microcrystalline cellulose (MCC), weighing machine, stack of sieves, mechanical sieve shaker

Procedure

1. 100g of lactose is weighed by using weighing machine.
2. The sieve nest in descending order (largest diameter to the smallest, from top to bottom) is prepared.
3. Lactose is poured onto the top of sieving nest.
4. The sieving machine is run for 10 minutes.
5. The weights of different sizes of lactose are weighed after the sieving process finished and a histogram is plotted for the distribution of size particle of lactose.
   
   
6. Step 1-5 are repeated for MCC.

Results

Lactose

Sieve diameter ( µm)	particle size range (µm)	Mass of lactose retained in each sieve (g)	Percentage of lactose retained (%)	Cumulative percentage retained (%)
<53	0 < x ≤ 53	8.139	8.139	8.139
53	53 < x ≤ 150	76.4572	76.457	84.596
150	150 < x ≤ 212	0.331	0.331	84.927
212	212 < x ≤ 300	12.7149	12.715	97.642
300	300 < x ≤ 500	0.0227	0.023	97.665
500	x > 500	1.412	1.412	99.077

MCC

Sieve diameter (µm)	Particle size range (µm)	Mass of microcrystalline cellulose (MCC)retained ineach sieve(g)	Percentage of microcrystalline cellulose (MCC)retained (%)	Cumulative percentage retained (%)
<50	0 < x ≤ 50	0.8598	0.8706	0.8706
50	50 < x ≤ 150	93.4919	94.6696	95.5406
150	150 < x ≤300	4.3167	4.3711	99.9113
300	300 < x ≤ 425	0.078	0.079	99.9903
425	x > 425	0.0096	0.0097	100

Questions

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

          For Lactose,the total mass is 99.0768 g.

          Average particle size: total mass/6          

                                            : 99.0768/6

                                            : 16.5128 g

          For MCC, the total mass is 98.7560 g

          Average particle size: total mass/5

                                            : 98.7560/5

                                            : 19.7512 g

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

    i.            Laser Diffraction

Laser diffraction is the one of the most widely used particle sizing techniques and has become the standard method in many industries for characterisation and control. This type of particle size analyser relies on the fact that particles passing through a laser beam will scatter light at an angle that is directly related to their size. When particle size decreases, the observed scattering angle increases logarithmically. Scattering intensity is also subject to particle size, diminishing with particle volume. What this means is that large particles scatter light at narrow angles with high intensity while small particles scatter at wider angles with low intensity.

Laser diffraction has a wide dynamic range, from 0.2 to 2000 microns and is very fast and reliable. It is also very flexible as it can be applied to dry powders, aerosols and emulsions. In addition, laser diffraction does not require calibration but can be easily verified.

  ii.            Dynamic Light Scattering

Sometimes referred to as Photon Correlation Spectroscopy or Quasi-Elastic Light Scattering, this method is a non-invasive and sensitive technique used for measuring the size of molecules and particles in the submicron region. The results are expressed as particle hydrodynamic diameter. Dynamic light scattering is an accurate, reliable and repeatable technique.

iii.            Sedimentation

This is a traditional method widely used in the paint and ceramics industries. Equipment as simple as the Andreason pipette or as complex as centrifuges and X-rays can be used in this method. The main advantage of this technique is that it determines particle size as a function of settling viscosity. However, as the density of the material is needed, this method is no good for emulsions where the material does not settle or for dense material that settles too quickly. It is also based on spherical particles, so can give large errors for particles large aspect ratio.

 iv.            Image Analysis

This technology generates data by capturing direct images of each particle, providing users with the ultimate sensitivity and resolution. Image analysis systems are capable of high-resolution sizing ranging from 0.5µm – 1000µm. Subtle differences in particle size and shape can be accurately characterised using this method.

   v.            Acoustic Spectroscopy

Instead of using light, this technique employs ultrasound for collecting information on the particles that are dispersed in fluid. This can be done because dispersed particles absorb and scatter sound waves similarly to light. Acoustic spectroscopy can be used to measure particle size distribution for any particle in a fluid system and can measure at very high particle concentrations.

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

The particle size distribution of active ingredients and excipients is an important physical characteristic of the materials used to create pharmaceutical products. The size, distribution and shape of the particles can affect bulk properties, product performance, accessibility, stability and appearance of the end product.

The link between particle size and product performance is well documented with regards to dissolution, absorption rates and content uniformity. Reducing particle size can aid the formulation of  normal curve equivalent’s with poor water solubility. Proper matching of active ingredient and excipient particle size is important for several process steps. Particle size analysis is an integral component of the effort to formulate and manufacture many pharmaceutical dosage forms.

Discussion

A sieve analysis is a practice or procedure used to assess the particle size distribution of a granular material. The size distribution is often of critical importance to the way the material performs in use. A sieve analysis can be performed on any type of non-organic or organic granular materials including sands, crushed rock, clays, granite, feldspars, coal, soil a wide range of manufactured powders, grain and seeds, down to a minimum size depending on the exact method. Being such a simple technique of particle sizing, it is probably the most common.

Sieve nest was prepared in descending order, from the largest diameter to smallest. In this experiment, 100 g of lactose or microcrystalline cellulose (MCC)was placed on uppermost sieve and sieving process was started. After 10 minutes, the sieving nest was removed and powder from each sieve was measured. The particle size of lactose and MCC is measured based on the principle that the particles cannot pass through certain sieve sizes due to the particle size larger than the sieve diameter.

From the result above, the particle size of lactose is estimated to be between 150µm to 300µm as the highest amount of lactose powder is retained at the sieve with diameter of 150µm. The particle size of MCC is estimated between 50µm to 150µm as the highest amount of MCC powder is retained at the sieve with diameter 50µm. Thus, we can draw a conclusion that lactose has bigger and more uneven particle size compared to MCC.

There are a few errors made in the experiment. There is loss of weight of lactose and MCC powder after sieving. For example, the initial weight of lactose before sieving is 100g, has reduced to 99.7475g after sieving and the initial weight of MCC before sieving is 100g, has reduced to 98.7560g. This may be due to some powders are blown out during the sieving process as the powders are light, some powders may stick to the sieve after the sieving process, small amount of powders may spilled out from the container when we moved it from one place to another place and the powders may not be completely removed from the sieves. Besides, the sieve net may be contaminated by other powders. Some powders are exposed to the air then absorb moistures and clump together. This affects the particle size distribution of the powders.

In order to reduce errors, a few precautions should be taken. First, when the sieve nest machine is operating, make sure the sieves are closed tightly so that the powders do not fly away or spill because of the high vibration of the machine. Besides, before conducting the experiment, the sieve net should be cleaned and dried to prevent contamination that will affect the result. We have to ensure we completely remove all the powder remained in each of the sieves. Last, the powders should be quickly poured into the sieve to minimize exposure to the air.

Conclusion

In this experiment,particle size distribution of powder and the size of solid particle of  lactose and microcrystalline cellulose (MCC) by sieve nest successfully determined.The size of particle is also determined.

References

• Jillavenkatesa A, Dapkunas S J, Lin-Sien Lum. 2001. Particle Size Characterization, NIST Special Publication
• Martin,A.N. 2006. Physical Pharmacy: Physical Chemistry Principles in Pharmaceutical Sciences. 5th Edition. Philadelphia: Lea & Febiger