FACULTY OF CHEMICAL PROCESS ENGINEERING TECHNOLOGY

Lab
PERFORM PARTICLE SIZE ANALYZER UNIT
01

BTP4253
PHARMACEUTICAL ANALYTICAL TECHNIQUES

Lab Objectives

By the end of this lab, we are able to:

1. Demonstrate sample preparation prior to particle size analysis (P4)

2. Operate particle size analyzer appropriately under supervision (P3)
3. Practice data analysis and data interpretation resulted from the
experiment (practical report) (P3)

Student names Student ID Section Group

20 NURIN FARHANA BINTI SHAMSOL TD17022 01G 2

FARAHAZWANI IZAZI BINTI MOHAMAD TD17023 01G 2

GOH YI LING TD17024 01G 2

NUR SYAFIQAH SAIDAH BINTI MOHD TD17025 01G 2

ROSLI
NOR AKMAL ADIBA BINTI JAMAL TD17027 01G 2

Delivery Date: 12th June

Due Date: 12th June 2020 2020
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1.0 INTRODUCTION

Particle size is an important attribute in APIs, solid oral drug products, and as a
critical quality attribute in semi-solids (suspensions) and sterile liquid products (injectables).
This is because it can influence important properties of the final product, such as the content
uniformity of tablets and the dissolution rate of the drug to the patient. Particle size analysis
has become a proxy for routine surface area measurement. However, context is important.
Therefore, representative sampling, sample homogeneity and particle morphology are
important because of the small sample sizes, potential settling of the sample. Particle size
reduction is a fast and cost-effective answer to increasing the exposure of poorly soluble oral
drugs by increasing surface area and thereby improving dissolution rate.

Then, particle size analysis is developed to characterize the size distribution of

particles in a sample. This analysis can also be used to measure the particle size of solid
materials, suspensions, emulsions, and aerosols. This help researcher and manufacturer to
control quality and determine the efficiency of a manufacturing process or the performance of
a final product.

All particle size analysis techniques report the particle size as a single number which
can be an issue when using shapes that are not a sphere. To overcome this issue, all particle
size analysis techniques relate a one-dimensional property of a particle to the size of an
“equivalent sphere”. This is done using measurements of surface area or volume, based on
the technique being used. The particle size analysis techniques available to measure the size
distribution of a particle include Laser Diffraction, Dynamic Light Scattering. Image Particle
Analysis and Acoustic Spectroscopy. There are many different particle size analysis
techniques, and the nature of the particle determines which technique is used. However, the
most broadly used technique is laser diffraction and dynamic light scattering.

Laser diffraction is extremely precise and repeatable measurements are attainable, but
understanding the limitations of this technique is critical to acquiring meaningful information.
It used as the standard technique in many industries, measures the light scattering when a
particle passes through a laser beam. The angle of scattered light is directly related to the
particle size where the larger particles scatter the light as narrow angles with high intensity
and smaller particles scatter the light at wider angles with low intensity. Laser diffraction has
a wide detection range (0.2–2000 μm) and is fast and reliable.
 BTP4253 PHARMACEUTICAL ANALYTICAL TECHNIQUES 3

In addition, for light scattering particle size analyzer, it is a non-invasive and sensitive
technique to measure the size of particles in suspension and molecules smaller than a micron
in a solution. During operation, a laser is shot through a polarizer and into a sample and the
light is scattered in all directions. The scattered light enters another polarizer where it is
collected by a photomultiplier and the resulting image is projected onto a screen, known as a
speckle pattern. This process is repeated, and the set of speckle patterns produced are
analyzed by an auto-correlator that compares the light intensity of each spot over time.
Varying mathematical approaches are used then to infer the autocorrelation data.

2.0 CHEMICALS/SOLUTIONS:

Cough syrup and Paracetamol

3.0 APPARATUS:

Cuvette, micropipette 10-100µl, micropipette tip 100 µl, test tube, syringe 1 mL and Particle
Size Analyzer unit.

4.0 PROCEDURE:

Solution preparation:

1. 1 mL Cough syrup solution was prepared with 5% v/v concentration and 19 mL of

pure water was used as dilution.

2. Then, paracetamol was prepared with 5% v/v concentration and 19 mL of pure water
was used as dilution.

3. The particle size analyzer unit was performed.

Particle size analyzer unit procedures:

1. Distilled water was used to clean the cell from any foreign solution by 1 mL of the
syringe and put it on the adaptor at the white side of the cell. Then, push the syringe slowly
into the flow cell.
 BTP4253 PHARMACEUTICAL ANALYTICAL TECHNIQUES 4

2. Next, the cough syrup was transferred to the cell by 1 mL syringe. Then, push the
syringe slowly into the flow cell on the adaptor at the white side of the flow cell.

3. The flow cell was closed with its lid.

4. The present of the bubble was checked.

5. The flow cell was clean with a tissue before enter the particle size analyzer unit.

6. The cell access button was pressed to open the lid, the lid will slowly raise allowing
access to the cell holder. The sample was transferred into the particle size analyzer unit and
closed the lid.

7. The software on the computer was opened and set up.

8. The software was connected to the particle size analyzer unit.

9. The start button was pressed and the result appeared.

10. The data was recorded.

11. The experiment was repeated with paracetamol solution with the same steps.

5.0 RESULT & DISCUSSION

Particle size analyzer is used to characterize the size distribution of particles in sample. From
this experiment, the Particle size analyzer is used to determine the diameter, intensity,
viscosity, concentration and seta potential for the sample. Particle size analyzer is based on
light scattering which is non-invasive techniques for characterizing nanomolecules of
particles in paracetamol solution and cough syrup. Both solutions were diluted twice with the
distilled water to adjust the concentration of the solution as the particle analyzer cannot read
the solution with the high concentration. The measure size will be inaccurate when the
concentration is too high due to the multiple scattering. The average readings of the cough
syrup solution and paracetamol solution from the particle size analyzer are calculated as
shown in Table 1 and Table 2.
 BTP4253 PHARMACEUTICAL ANALYTICAL TECHNIQUES 5

Table 1: particle size analyzer of cough syrup solution

No. Viscosity Intensity Diameter Concentration Zeta

(cP) (Cnt/s) (nm) (mg/mL) potential
(mV)
Reading 1 0.9 1300675 2.2 0.00 -27.27
Reading 2 0.9 1318337 3.0 0.00 -28.37
Reading 3 0.9 1309595 1.4 0.00 -27.45
Average 0.9 1309536 2.2 0.00 -27.70

Table 1: particle size analyzer of paracetamol solution

No. Viscosity Intensity Diameter Concentration Zeta

(cP) (Cnt/s) (nm) (mg/mL) potential
(mV)
Reading 1 0.9 499360 1542.2 0.00 -9.30
Reading 2 0.9 1133299 745.2 0.00 -11.20
Reading 3 0.9 1706845 1537.6 0.00 -10.70
Average 0.9 1113168 1275.0 0.00 -10.40

The result for zeta potential in this experiment can related to the stability of the solution.
Based on the theoretical, zeta potential for solution particle should be ±40 to ±60 in order to
obtain good degree of stability. The average reading of the zeta potential on cough syrup is a
bit higher than zeta potential of paracetamol solution. As the zeta potential of the cough syrup
is -27.70 and zeta potential for paracetamol solution is -10.40 it is not in the range of
theoretical value. It can be concluded that the cough syrup and paracetamol solution are not
stable.

6.0 CONCLUSION

In conclusion, particle size analysis of two different sample of cough syrups and paracetamol
has been successfully demonstrated. Generally, this particle size analysis is performed to
determine the nanoparticle size of the samples as well as its Zeta Potential. Based on the
results above, it shows that the results did not meet the range of theoretical values due to
some errors might occur while doing the experiments. Some errors might be the changes in
particle sizes and structures of the sample as it can highly influence the pharmacological
behaviour of drug product. Smaller the particles, greater the diffusion coefficient and it is
 BTP4253 PHARMACEUTICAL ANALYTICAL TECHNIQUES 6

depended by with zeta potential values. Hence, this reasons might be one of the possibility of
the zeta potential values did not reach within the range of theoretical values.

7.0 REFERENCES

Ata Scientific Instruments. 2020. BASIC PRINCIPLES OF PARTICLE SIZE ANALYSIS.

[online] Available at: https://www.atascientific.com.au/basic-principles-of-particle-
size-analysis/ [Accessed 12 June 2020].

Basic principles of particle size analysis. Retrieved from

https://www.atascientific.com.au/basic-principles-of-particle-size-analysis/

Elder, D., Pacowski, G., Nelson, P. and Tindal, S., 2020. The Importance Of Particle Size
Analysis. [online] European Pharmaceutical Review. Available at:
https://www.europeanpharmaceuticalreview.com/article/70846/importance-particle-
size-analysis/ [Accessed 12 June 2020].

Intal. P & et al. (2016). Particle Size Analysis of Soils. Retrieved from
https://www.academia.edu/28124221/Particle_Size_Analysis_of_Soils

Oehmig, R., 1992. Principles, methods, and application of particle size analysis. Earth-
Science Reviews, 33(1), pp.59-61.

Samuel Mckenzie, B., 2020. Particle Size Analysis Techniques. [online] News-Medical.net.

Available at: https://www.news-medical.net/life-sciences/Particle-Size-Analysis-
Techniques.aspx [Accessed 12 June 2020].