Practical 4: Particle size analysis (Part A)

TITLE

Sieving

DATE

16 November 2015

OBJECTIVE

-determine the particle size distribution of a powder

-determine the size of a particle.

INTRODUCTION

A sieve analysis is a practice or procedure are use 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, coal, soils, a wide range of manufactured powders, grain and seeds, down to a minimum size depending on the exact method.  Sieves are commonly used to break down agglomerates and determine the use and size distribution of a particular powder. In this practical, we are required to used a sieve nest to determine the particle size and size distribution of two common excipients used in tablet formulations, namely lactose and microcrystalline cellulose (MCC).

APPARATUS AND MATERIAL

Lactose, microcrystalline cellulose (MCC), weighing machine, stack of sieves, sieve nest, weighing boat.

PROCEDURE

1. 100g of lactose was weighed.
2. The sieve nest was prepared in the descending order (largest diameter to the smallest, from top to bottom)

3. The powder was placed at the uppermost sieve and the sieving process was allowed to proceed to 20 minutes.
4. Upon completion, the powder collected at every sieve was weighed and the particle size distribution was plotted in the form of a histogram.
5. The process above was repeated by using MCC.

RESULT

Size /diameter of aperture( µm )	Particle size range (µm )	Weight of microcrystalline cellulose(MCC) (g)	Weight of lactose (g)
<50	0 < x≤ 50	21.7584	2.2125
50	50 ≤x≤ 150	62.3678	10.1738
150	150 ≤x≤ 200	5.4169	30.0951
200	200 ≤x≤ 425	4.7528	52.6521
425	425≤x≤500	2.1459	1.6280
500	>500	1.6593	1.1520
TOTAL		98.1011	97.9139

QUESTIONS

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

For lactose, the average particle size is 200 µm while for MCC is 50 µm.

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

i) Laser diffraction analysis

Also known as laser diffraction spectroscopy, is a technology that utilizes diffraction patterns of a laser beam passed through any object ranging from nanometers to millimeters in size to quickly measure geometrical dimensions of a particle. This process does not depend on volumetric flow rate, the amount of particles that passes through a surface over time.

ii) Microscopy

Perhaps the most obvious and accurate method for determining the particle size and shape characteristics of a small sample is microscopy. Unfortunately the operator time required to analyse a sufficient number of particles to be representative is prohibitive except in the highest value applications. This is an offline method of particle characterisation with very limited throughput which may make it unsuitable for a number of applications.

iii) Coulter counter

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

iv) Backlight Imaging

Backlight imaging is a relatively new technology in the area of particle sizing and characterisation. Put simply, particles are transported (usually by gravity) between a light source and one or more cameras. The resultant images are analysed to determine the sizes of the individual particles, which are combined to create the overall particle size distribution. This method allows for large size ranges to be measured, but provides little shape information on particles. As the images appear as silhouettes on a back background no particle morphology information is obtainable.

v) Imaging particle analysis

Is a technique for making particle measurements using digital imaging one of the techniques defined by the broader term particle size analysis. The measurements that can be made include particle size, particle shape (morphology or shape analysis and grayscale or color, as well as distributions (graphs) of statistical population measurements.

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

In solid or suspension delivery systems, dissolution and solubility characteristics are often controlled by particle size, and it is clear that dissolution and solubility have an impact on bioavailability of active ingredients.

In suspensions, the physical characteristics of the fluid and the size of particles both have an effect on precipitation and aggregation. In practice, finer particles generally make for a more stable suspension. That said, stability can also depend on the balance of the repulsive and attractive forces that exist between particles as they approach one another. If the particles have little or no repulsive force then eventually there will be some manifestation of this instability, such as aggregation.

Particle size may also affect the behavior of a formulation during processing and, ultimately, its content uniformity. In direct compression tableting, for example, particle size can influence segregation behavior, the ease with which powder flows through the press and the compressibility of a formulation.

Particle size also has a critical effect on the content uniformity of solid dosage forms, and it often matters to create the right relationship between the size and densities of API and excipient particles.

Similarly, the size of particles can affect viscosity and flow, and increasing the polydispersity of particle sizes in a powder can improve its flow properties. For example, for many powders subject to flow in an industrial process, a bimodal distribution of particle sizes ensures easier flow during processing.

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 employs a woven, punched or electroformed mesh, usually in brass or stainless steel, with known aperture diameters which form a physical barrier to particles. Most sieve analyses utilize a series, stack or 'nest' of sieves, which has the smallest aperture (50 µm) above a collector tray followed by meshes with progressively larger aperture (150, 200, 425, 500 µm) towards the top of the series. Powder is loaded on to the coarsest sieve of the assembled stack and the nest is subjected to mechanical vibration. After a suitable time the particles are considered to be remained on the sieve mesh with an aperture corresponding to the sieve diameter.

Based on the result of the experiment, the weight of the MCC obtained is the highest at the range of particle size 200 ≤x≤ 425 µm which is 52.6521 g. While for the lactose, the highest weight is obtained at the finer particle size range of 0<x≤50 µm with the value of 62.3678 g. It is known that if the particles cannot pass certain sieves, 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 as they are two different materials with different physical properties.

There are some possible sources of error while conducting this experiment as the total weight of lactose and MCC originally are not equivalent to the weight of powders obtained in individual sieves after being summed up. This could be due to the situation there is still amount of powder left in the sieves after the process was carried out.  Besides that, some of powders are spilled out from the container since the machine is not closed correctly which will affect the result obtained.

Therefore, before conducting this experiment certain measures should be taken which include the steps of making sure the sieves are cleaned by using brush because to remove any soil particles that may be stuck at the openings and also the need to set up the machine in the correct manner to avoid any problem in handling it throughout the sieving process.

CONCLUSION

From the graph obtained, it is made to be known that the particles size of MCC is smaller than lactose. Thus, we can conclude that although sieving process is an old technique, but it enables the size of solid particles and its distribution to be analysed. This analysis helps in formulation of efficacious medicines as well as their pharmacodynamics properties for desirable therapeutic effect.

REFERENCES :

1.  Michael E. Aulton, 2007, Aulton's Pharmaceutics The Design and Manufacture of Medicines, Third Edition, Churchill Livingstone Elsevier.
2.  Patrick J Sinko ,PhD, RPh, Martin's Physical Pharmacy and Pharmaceutical Sciences, 6th Edition, Lippincott Williams and Wilkins.