EXPERIMENT: SEIVING

TITLE: Sieving

OBJECTIVE: To determine the size and size distribution of lactose and microcrystalline cellulose (MCC).

INTRODUCTION:          A test sieve is a measuring instrument which is used to measure the particle size. They are made with only the highest quality materials and are available in diameter sizes of 38, 100, 150, 200, 250, 300, 315, 350, 400 or 450 mm as well as in 3, 8, 12 or 18 inches.          The sizes of solid particles from 125mm down to 20 microns can be measured efficiently by standard test sieve. A test sieve 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.

       In this experiment, two excipients used in tablet formulations, namely lactose and microcrystalline cellulose (MCC) are given to measure its particle size and measure the size distribution by using the test sieve. The diameter size of test sieve we are using in the experiment are 50, 150, 200, 300 and 425mm.

APPARATUS:
Sieve nest, weighing boat, analytical balance 

Sieve nest 

CHEMICALS:
Lactose, microcrystalline crystal (MCC)

EXPERIMENTAL PROCEDURE:

1. A 100g of Lactose powder was weighed. 
   
2. The sieve nest was prepared in descending order where the top being the largest in diameter and the bottom being the smallest in diameter. 
   
3. The powder was then placed at the uppermost sieve and allowed the sieving process to proceed for 10 minutes. 
   
    
4. Upon completion, the powder that was collected at each sieve was weighed and a particle  size distribution was plotted in a histogram. 
5. The process was repeated using Microcrystalline Cellulose(MCC).

RESULT :

Diameter of sieve (µm)	Range of size of lactose (µm)	Weight of lactose(g)
<50	0-50	3.7975
50	50-150	93.7331
150	150-200	1.4084
200	200-300	0.8361
300	300-425	0.0091
425	>425	0.0059
Total		99.7901

Graph of weight of lactose against size of lactose

Diameter of sieve (µm)	Range of size of microcrystalline cellulose, MCC (µm)	Weight of microcrystalline cellulose, MCC(g)
<50	0-50	52.4928
50	50-150	40.4162
150	150-200	3.3123
200	200-300	1.8172
300	300-425	0.1300
425	>425	0.0823
Total		98.2508

Graph of MCC against MCC size  

QUESTIONS:

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

Base on the result obtained, the average particle size for lactose is 100µm and the average particle size for MCC is 25µm.

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

Other methods to determine the size of particles are sedimentation, elutriation, using a Coulter counter and Dynamic light scattering. 
Sedimentation is the tendency for particles in suspension to settle out of the fluid in which they are entrained, and come to rest against a barrier. This is due to their motion through the fluid in response to the forces acting on them(gravity, centrifugal acceleration or electromagnetism). Settling is the falling of suspended particles through the liquid, whereas sedimentation is the termination of the settling process. Sedimentation may pertain to objects of various sizes, ranging from large rocks in flowing water to suspensions of dust and pollen particles to cellular suspensions to solutions of single molecules such as proteins and peptides. Even small molecules are able to supply a sufficiently strong force to produce significant sedimentation. The term is typically used in geology, to describe the deposition of sediment which results in the formation of sedimentary rock, and in various chemical and environmental fields to describe the motions of often-smaller particles and molecules. Process is also used in biotech industry to separate out cells from the culture media. 
Elutriation is a process for separating particles based on their size, shape and density, using a stream of gas or liquid flowing in a direction usually opposite to the direction of sedimentation. This method is mainly used for particles smaller than 1 μm. The smaller or lighter particles rise to the top (overflow) because their terminal sedimentation velocities are lower than the velocity of the rising fluid. The terminal velocities of any particle in any medium can be calculated using Stokes' Law. 

A Coulter counter is an apparatus for counting and sizing particles suspended in electrolytes. It is used for cells, bacteria, prokaryotic cells and virus particles. A typical Coulter counter has one or more micro-channels that separate two chambers containing electrolyte solutions. As fluid containing particles or cells is drawn through each micro-channel, each particle causes a brief change to the electrical resistance of the liquid. The counter detects these changes in electrical resistance. 

Coulter counter

Dynamic light scattering, also known as photon correlation spectroscopy or quasi-elastic light scattering, is a technique in physics that can be used to determine the size distribution profile of small particles in suspension or polymers in solution.  It can also be used to probe the behavior of complex fluids such as concentrated polymer solutions.

Dynamic Light Scattering

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

The particle size distribution of active ingredients is an important physical characteristic of the materials used to create pharmaceutical products. The size, distribution and shape of the particles can affect the rate of reactions, potential to dissolve, packing density, sedimentation, effectiveness of drug delivery(inhalation), product appearance and texture. 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 NCE’s with poor water solubility. Proper matching of active ingredient and particle size is important.

a) Rate of reactions

When it comes to solids, the surface area of the particle is critical in determining the rate of chemical reaction. Chemical reactions are far more likely to occur in fine particles than otherwise. A great example of an industry reliant on this principle is the cement industry, which must deliver the appropriate reaction rate in order to achieve the desired product.

b) Potential to dissolve

The effect of particle size on dissolution rate is similar to the influence of particle size on the reaction rate. By creating finer particles and therefore increasing surface area, the physical barriers to dissolution are weakened, making the process occur much more quickly. Put simply, finer particles are more likely to dissolve quicker. The pharmaceutical industry knows the importance of this, as the speed of dissolution has direct effects on bioavailability and, therefore, the effectiveness of any given drug.

c) Packing density

The efficiency with which particles pack together is crucial to many industries as well. As a rule, large particles are going to pack more poorly than small particles. By decreasing the particle size, packing density is improved and voidage (unoccupied volume) is reduced. This is particularly important in production of metals through mould filling, as unoccupied volume can create a significantly flawed product.

d) Sedimentation

Suspension “stability” is most easily achieved buy avoidance of sedimentation (ie. the tendency of particles in suspension to settle out of the fluid). In order to ensure stability, the gravitational pull exerted on particles must be balanced with the “up-thrust” of the fluid. Unstable suspensions can wreak havoc in the food industry, for example, where consistency is essential to product perception.

e) Effectiveness of drug delivery by Inhalation

In order to maintain the integrity of air supply in the body, our respiratory systems are incredibly efficient at filtering out particles above a certain size. This stops these particles from entering and damaging the lungs. Orally or nasally inhaled drug manufacturers must ensure the product is capable of penetrating the lungs; conversely, cleaning product manufacturers may need to provide extra controls in order to prevent inhalation if particles are of a dangerous size.

f) Product appearance

The principle behind the particle size analysis technique of laser diffraction is that particles will scatter light in different ways depending on their size. In some industries, however, this principle is important not just for analysis but also for end product — paint manufacturers, for example, must achieve desirable light scattering effects in order to define parameters such as hue, tint, transparency, gloss and so forth.

g) Texture

Overall, the size of particles can have direct correlation with a customer’s perception of a product and, therefore, the reputation of a manufacturing company. This is particularly true in the case of food products in which particle size can impact the enjoyment of the product; take coffee, for example, with which particle size affects the flavours released in the brewing process.

DISCUSSION :

          In this experiment, 100g of lactose and microcrystalline cellulose (MCC) powders are placed on the sieve nest and are sieved for 10 minutes using a sieve shakers and the particle size distribution of both powder are determined. There is a total of five sieve nests used and they ae arranged in a descending order of their diameter, which the sieve nest with largest diameter is placed on the top, whereas the sieve nest with the smallest diameter is placed on the bottom.

         When lactose is sieved, the lactose that obtained in the sieve with diameter of 300µm and 425µm are very less, which are 0.0091g and 0.0059 g respectively. This means that the size of lactose particle is finer. The lactose obtained in the sieve with diameter of 50µm is the most. This shows that the lactose mostly remain at size of 50-150µm. For microcrystalline cellulose, the weight of MCC of size 0-50µm and 50-150µm is the largest, which are 52.4928g and 40.4162g respectively. This means that the size of MCC is normally exist in the range of 0-150µm.

        The total of the weight of lactose and MCC obtained is not the same as their original weight due to some errors such as the effect of the surrounding air which cause some of the lactose and MCC to be blown off when they are transferred from the sieve to the weighing board. There are also some precaution steps that need to be taken during the experiment. Make sure that the sieve shaker is set up properly before starting the sieving process.

CONCLUSION :

       Sieve method can be used to determine the particle size and size distribution of a powder. The normal range of size of lactose is 50-150µm, whereas the normal range of size of microcrystalline cellulose (MCC) is 0-150µm.