Practical 4-Sieving (Part A)

PRACTICAL 4: SIEVING

PART A

Title:

Particle Size and Size Distribution.

Objective

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

Date

17th November 2014.

Introduction

            Sieving is a process of using an instrument with a meshed or perforated bottom, used for separating the coarse part from the fine part of loose matter, for straining liquids and so on, especially one with a circular frame and fine meshes or perforations. Sieve analysis is used to obtain the particle size distribution of a solid material by determining the amount of powder retained on a series of sieves with different sized apertures.

Particles are three-dimensional objects. In order to provide a complete description of a particle, three parameters are required — length, breadth and height. Thus, it is impossible to describe a particle using a single number that equates to particle size. Therefore, most sizing techniques assume that the material being measured is spherical because a sphere is the only shape that can be described by a single number, its diameter, thus simplifying the way particle size distributions are represented.

In this practical, lactose and microcrystalline cellulose, two common excipients used in tablet formulations are used. Powder form of lactose can be graded depending on particle size distribution, density and how easily it flows. The properties of lactose that makes them suitable as a pharmaceutical filler in tablets and capsules are cost effective, highly available, physically and chemically stable and are able to form tablets under compression. Lactose wettability enables it to form a dissolved layer around drug and retard the drug dissolution rate.

Microcrystalline cellulose is a commonly used excipient in the pharmaceutical industry. It has excellent compressibility properties and is used in solid dose forms, such as tablets. Tablets that are formed are hard but dissolve quickly. Microcrystalline cellulose is the same as cellulose, except that it meets USP standards. It is also found in many processed food products, and may be used as an anti-caking agent, stabilizer, texture modifier, or suspending agent among other uses. According to the Select Committee on GRAS Substances, microcrystalline cellulose is generally regarded as safe when used in normal quantities.

Experimental Method

Chemicals

Lactose powder and microcrystalline cellulose (MCC).

Apparatus

Beaker, weighing boat, laboratory test sieve (with 425μm, 300μm, 200μm, 150μm, 53μm sieve nest), spatula, electronic balance and electrical motorized sieve shaker (Octagon 2000 digital sieve shaker).

Procedures

1. 100g lactose was weighed.

2. The sieve nest was prepared in 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 for 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 above process was repeated using MCC.

Results

1)      Lactose

Sieve opening	Mass of lactose remained in each sieve/ g ( W sieve)	% retained = (W sieve/ W total) x 100%	Cumulative % retained	% passing= 100% - cumulative % retained
< 53 µm	0.7625	(0.7625/100) x 100% = 0.7625%	0.7625	100 – 0.7625= 99.2375
53 µm	18.7789	(18.7789/100) x 100% = 18.7789%	0.7625 + 18.7789 = 19.5414	100 – 19.5414 = 80.4586
150 µm	48.9482	(48.9482/100) x 100% = 48.9482%	19.5414+48.9482 = 68.4896	100 – 68.4896 = 31.5104
200 µm	0.7261	(0.7261/100) x 100% = 0.7261%	68.4896 + 0.7261 = 69.2157	100 – 69.2517 = 30.7483
300 µm	8.6303	(8.6303/100) x 100% = 8.6303%	69.2157+ 8.6303 = 77.8460	100 – 77.8460 = 22.1540
425 µm	22.0313	(22.0313/100) x 100% = 22.0313%	77.8460+22.0313 = 99.8773	100 – 99.8773 = 0.1227

Theoretical weight of lactose = 100g

Experimental weight of lactose:

0.7625+ 18.7789 + 48.9482+ 0.7261 + 8.6303 + 22.0313 = 99.8773 g

Mass loss during sieving : (100 – 99.8773) / 100 x 100 = 0.12 %

2)      MCC

Sieve opening	Mass of MCC remained in each sieve/ g ( W sieve)	% retained = (W sieve/ W total) x 100%	Cumulative % retained	% passing= 100% - cumulative % retained
<53 µm	3.7321	(3.7321/100) x 100% = 3.7321%	3.7321	100 – 3.7321 = 96.2679
53 µm	89.6964	(89.6964/100) x 100% = 89.6964%	3.7321+89.6964 = 93.4285	100 – 93.4285 = 6.5715
150 µm	4.0674	(4.0764/100) x 100% = 4.0764%	93.4285+4.0764 = 97.5049	100 – 97.5049 = 2.4951
200 µm	1.6289	(1.6289/100) x 100% = 1.6289%	97.5049+1.6289 =99.1338	100 – 99.1338 = 0.8662
300 µm	0.0957	(0.0957/100) x 100% = 0.0957%	99.1338 +0.0957 = 99.2295	100 – 99.2295 = 0.7705
425 µm	0.0018	(0.0018/100) x 100% = 0.0018%	99.2295 + 0.0018 = 99.2313	100 – 99.2313= 0.7687

Theoretical weight of MCC = 100g

Experimental weight of MCC:         

3.7321 +89.6964 + 4.0674 + 1.6289 + 0.0957 + 0.0018 = 99.2313 g

Mass loss during sieving : (100 – 99.2313)/100 x 100 = 0.77%

Questions

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

The average particle size is less than 150 µm for both lactose and MCC. This is because most of the lactose and MCC powder were found in the sieve nest with aperture size of less than 150 µm.

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

•         Aerodynamic method (APS, Impactors, etc)
•          Optical method (optical counters, light scattering analyzers, etc)
•           Electrical sensing zone method (Coulter Counter)
•           Electrical mobility and condensation method (DMA+CNC)
•           Electron microscopy 

3. What is 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. Take, for example, the widespread operation of direct compression tableting; particle size can influence segregation behaviour, the ease with which powder flows through the press and the compressibility of a formulation. In turn, these factors affect the consistency of tablet weight and composition, how the press operates and the mechanical properties of the finished product.

Discussion

Sieve analysis is one type of mechanical analysis which determines the size range of particles present in lactose and microcrystalline cellulose (MCC), expressed as a percentage of the total dry weight or mass. Sieve analysis consists of shaking the lactose sample through a set of sieves that have progressively smaller openings. As a stack of sieves are prepared, the sieve that has larger opening size are placed above the ones that having smaller opening size. This means that the sieve that has diameter of aperture of 425 µm will be placed above followed by 300 µm, 200 µm, 150 µm, 53 µm and <53 µm. 

Theoretically, the smaller the size aperture of the sieve nest, the more the powder we can get from the sieve nest. From the mass of powder remained in each sieve nest, we can calculate the retained percentage as well as passing percentage. By comparing both the graph of MCC and lactose, we know that the particle size of MCC is smaller than lactose. It seems that MCC is affected more than lactose due to the physical vibration that has been applied on the particles, since the hardness of the surface of the particle contributes to the reduction of particle size. The results from this experiment were slightly inaccurate as the weight of lactose and MCC was inaccurate since there was still some powder left in the sieves after the process is carried out.  Besides that, some of powders may have spilled out from the container since the machine was not closed correctly. This also affects the result obtained.

The results of sieve analysis were generally expressed as the percentage of total weight of lactose and MCC that passed through different sieves. From the results, the total mass sample after sieving was smaller than the total mass before sieving where 0.1227 g and 0.7687 g were lost. This is probably because the small particles of lactose and MCC were lost when the sieves were being vibrated. The lactose and MCC used were then collected back and weighed. It was found that after sieving, there were 0.12 % and 0.77% loss of lactose and MCC respectively.

Therefore, the total mass was corrected by adding the mass retained with the corrected mass of lactose and MCC. In the formulation, the uniformity of the particle size of the powder and also the roundness play important roles in the pharmacodynamic properties of the medicine. It will affect the absorption rate and stability of the formulation.

Conclusion

Based on the histogram graph, we can conclude that the particle size of MCC is smaller than lactose. It was proven when the cumulative percentage retained for lactose was 99.8773% while the cumulative percentage retained for MCC was 99.2313%.

Reference

Pa

Particle Size Is Important: Particle Analysis Techniques. http://www.pharmaceutical-int.com/article/particle-size-is-important-particle-analysis-techniques.html [12^th December 2014].

Sieve Analysis Test. http://www.uta.edu/ce/geotech/lab/Main/sieve/index.htm#sthash.WEysNnzz.dpuf [12^th December 2014].