PARTICLE SIZE and SHAPE ANALYSIS using MICROSCOPE

Date:20/11/2014

Title

Particle Size and Shape Analysis using Microscope

Objective

To analyze and interpret the shape of particles and to observe and compare the size of particles under microscope.

Introduction

Usually, in handling and processing operations in many powders the size of particle plays important key role in determining the bulk properties of the powder. Powders’ particles have many range of sizes and shapes and each of them different to each other. Determine the size of particles is really important in achieve an optimum production of efficacious medicines.When synthetizing and formulating a medicine, the particle size of the drug and other powder is determined because this willinfluences the subsequent physical performance of the medicine and the pharmacological of the drug. In order to obtain an equivalent and accurate diameter, there are a few methods in analyzing and interpreting the size of particle. One of them is by using the microscope. The size, shape, surface area and arrangement of the particles can be analyzed by using this method. In this experiment, various type of sands ( 150µ, 355µ, 500µ, 850µ, mixed ) and two different powders ( MCC and lactose ) are given to be analyze.

Materials

Sands( 150µ, 355µ, 500µ, 850µ, mixed )

Lactose powder

MCC powder

Apparatus

Microscope

100 ml beaker

Spatula

Glass slide and cover slip

Procedure

1. Sands with sizes of 150µ, 355µ, 500µ, 850µ, mixed, lactose and MCC are put in the different beakers using spatula. The beakers are labelled according to the content.

2. The microscope was set up and ready to be use.

3. 150µ sand scattered on the glass slide and covered with the cover slip.

4. The sand was observed under the microscope using 4x100 magnification.

5. The particles were observed microscopically and the shape was determined.

6. Steps 3 to 5 were repeated by using 355µ, 500µ, 850µ, mixedsands, lactose and MCC powder.

Result

Various sizes sand

The sand under the microscope is various in sizes and has different colour. The size of the sand is not fixed and has different shapes. Most of the sand has shape edges.

150 mic

The sand under the microscope all has almost same size. They are all small size with different shapes and different colour.

355 mic

The sand under microscope all has almost the same size. Although they have different shapes, all of them have shape edges.

500 mic

Sand with 500 mic has bigger in size. They have almost the same size but different colour. Their shapes are different with many sharp edges.

850 mic

Sand with 850 mic has the biggest size compare to others. We can see it easily and clearly under microscope, though they have different size and colour. But they have shape edges and some of them are slightly transparent.

Lactose

The size of lactose is very fine. The shape of lactose cannot be seen clearly under microscope.

MCC

The size of MCC is very fine, the size cannot be observed easily under the electronic microscope.

Questions

Explain in brief the various statistical methods that you can use to measure the diameter of particle.

The particle that has same size of sphere with same diameter is known as mono-size. However, most of the sand consists of different size and shape. The size of distribution can be broken down into different size ranges. The frequency which can be presented using histogram or cumulative frequency form is used to present the size of distribution of size of sand. There will be three types of result shown by the histogram which are normal distribution, positively skewed distribution and bimodal distribution. The cumulative frequency usually used to indicate the undersize of oversize sand.

The know the mode and median diameter of the particle size, it still can be obtained from the incomplete particle size distribution while the mean can only be obtained through the complete particle size distribution with the upper  and lower limit known. There are several ways to determine the particle size. One of the ways is by using Arithmetic mean. Arithmetic mean can be calculated by summating a particular parameter for all the individual particles in a sample and dividing the value achieved by total number of particles. The next way is Geometric mean. It follows a log-normal distribution. The last one is interconversion mean. It can be obtained by using Hatch-Choate equations.

2. State the best statistical method for each of the samples that you have analysed.

The best statistical method is by using histogram.

DISCUSSION

In this experiment ,it can be seen that the sands have various shapes and sizes.The sizes of the sands increases from the 355 µm, 500 µm, to 850 µm respectively.  It is also can be seen that the shapes of the sands are irregular,rough surfaces and has sharp edges.While the lactose has similar and small size.Lactose also exhibit regular shapes and it is seen mostly to be round and do not have sharp edges.

To observe the shapes and sizes of the sands and lactose,we use microscope which can magnify and resolute the image.Microscope is a valuable instrument inlaboratory.We put the sample of particle on a slide and observe it under the microscope. Light traveling up from the mirror passes through the glass slide, specimen, and cover slip to the objective lens  (the one closest to the object). This makes the first magnification: it works by spreading out light rays from the specimen so they appear to come from a bigger object. In this experiment,we use low power objective (10X), one of the shortest objective lenswhich is probably the most useful lens for viewing slides.  The low power objective is always safe to use as it cannot be lowered to the point of contacting and thus possible breaking a slide. 

By far the most important physical property of particulate samples is particle size. Particle size measurement is routinely carried out across a wide range of industries and is often a critical parameter in the manufacture of many products. Particle size has a direct influence on

material properties such as reactivity or dissolution (catalyst,paints),stability in suspension (sediment) and appearance(powder coating and inks).Measuring particle size and understanding how it affects your products and processes can be critical to the success of many manufacturing businesses.

As well as particle size, the shape of constituent particles can alsohave a significant impact upon the performance or processing of particulate materials. Many industries are now also making particles shape measurements in addition to particle size in order to gain a better understanding of their products and processes. Some areas where particle shape can have an impact include reactivity and solubility (pharmaceutical activities),powder flow and handling(drug delivery system) and texture and feel (food ingredients).Particle shape can also be used to determine the state of dispersion of particulate materials, specifically if agglomerates or primary particles are present

Conclusion

In a conclusion, different type of sand has different shape and size. They have one similarity which is most of them having shape edges. All of them have irregular shape. Hence, granulation is very important to ensure the drug can flow smoothly in pharmaceutical industry.

REFERENCES

1.http://en.wikipedia.org/wiki/Microscope

2.microscope.org/basic/microscope-parts.htmhpts/chpt1/intro1.html

3.http://golik.co.il/Data/ABasicGuidtoParticleCharacterization(2)_1962085150.pdf

Sieving

DATE OF EXPERIMENT :20/11/2014

TITLE:Sieving

OBJECTIVES:   

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

b) To determine the size of particles.  

APPARATUS AND MATERIALS:

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

INTRODUCTION:

                 Sieves are commonly used to break down agglomerates, and determine the size and size distribution of a particular powder. 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.In this practical, students are given two common excipients used in tablet formulations, namely lactose and microcrystalline cellulose (MCC). Students are required to use a sieve nest to determine the particle size and the size of distribution of both powders.

PROCEDURE:

1.      100g of lactose is weighed by using weighing machine.

2.      Sieve nests in the order of increasing size and appropriate size of sieving are prepared.

3.      Lactose is poured onto the top of sieving nest.

4.      The sieving machine is run for 20 minutes.

5.      The weights of different sizes of lactose are weighed after the sieving process finished and a graph is plotted for the distribution of size particle of lactose.

6.      Step 1-5 are repeated for MCC.

RESULTS:

Diameter of aperture (μm)	Particle size (μm)	MCC		Lactose
		Weight (g)	Frequency (%)	Weight (g)	Frequency (%)
<45	0<x≤45	10.4452	10.8072	5.1816	5.2251
45	45<x≤150	82.3946	85.2499	78.2475	78.9043
150	150<x≤300	3.7004	3.8286	0.2014	0.2031
300	300<x≤425	0.1067	0.1104	14.1168	14.2353
425	425<x≤500	0.0008	0.0008	0.0424	0.0428
500	>500	0.0030	0.0031	1.3779	1.3895
Total =                    96.6507g                                         99.1676g

QUESTIONS & ANSWER:
1. What are the average particle size for both lactose and MCC?

The average particle size for both lactose and MCC is between 45-150μm.

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

Microscopy, sedimentation techniques, optical and electrical sensing zone method, laser light scattering techniques, and surface area measurement techniques.

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

The size, and hence the surface area of a particle, can be related to the physical, chemical and pharmacologic properties of drugs. Clinically, the particle size of a drug can affect its release from dosage forms that are administered orally, parenterally, rectally and topically. The successful formulation of suspensions, emulsions and tablets; both physical stability and pharmacologic response also depends on the particle size achieved in the product.

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, processability, 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 NCE’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. HORIBA Instruments can provide both the analytical tools and technical support required to help pharmaceutical companies characterize their particulate systems with confidence.


DISCUSSION:
Even though the experiment above was successful but the results are not very accurate due to some errors that occur throughout the experiment. As we can see, the total mass of lactose and MCC before and after sieving is not the same. This is due to some of the particles being stuck in the sieve and also the sides of the container. Next, when obtaining the lactose and MCC from the sieves, some of the particles have dropped to the surroundings and hence lost in the process. Therefore, an inaccurate value of mass for the particle size ranges are obtained. The analytical balance that is not calibrated well is also one of the causes for inaccurate readings.

CONCLUSION

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

REFERENCE:

1. cma.tcd.ie/misc/particle.ppt
2. Martin's Physical Pharmacy and Pharmaceutics 6th Edition.
3. http://www.horiba.com/scientific/products/particle-characterization/applications/pharmaceuticals/

Mutual Solubility Curve for Phenol and Water

DATE OF THE EXPERIMENT:4/11/2014

TITLE:  Phase Diagram – Mutual Solubility Curve for Phenol and Water.

OBJECTIVES:   

a) to measure the miscibility temperature of several water and phenol mixtures

b) to determine the mutual solubility curves of phenol and water.

APPARATUS AND MATERIALS:

Measuring cylinder, thermometer, beaker, boiling tube, distilled water, phenol, water bath

INTRODUCTION:

                     

          

            

     Phenol known as carbolic acid, hydroxybenzene  and phenyl alcohol, is produced at the rate of millions of tons per year, mostly from isopropyl benzene. Phenol is a starting material in the manufacturer of plastics and drugs. It was used an antiseptic beginning in the 1860’s. However, phenol is poisonous. The phenol-water mixtures used in this lab are concentrated and dangerous by contact or ingestion. Aqueous phenol solutions have been used pharmaceutically. At low and high percentages of phenol , water and phenol mix completely, forming a single liquid phase. Above the critical temperature, phenol and water are completely miscible. The water- phenol phase diagram contains a solid phase at high percent phenol, near and somewhat above room temperature. That part of the diagram is not shown in the figure. The independent variable in the phase diagram is composition. Composition is sometimes given as mass percent. This experiment will refer to composition as mole fraction phenol.

       Generally, both liquids become more soluble with rising temperature until the critical solution temperature or consolute point is attained, and above this point the liquids become completely miscible. There is a big possibility that any  pair of liquids can form a closed system, whereby both upper and lower critical solution temperature exist, however it is not easy to determine both the temperature except for nicotine and water. At any temperature below the critical solution temperature, the composition for two layers of liquids in equilibrium state is constant and does not depend on the relative amount of these two phases.

PROCEDURE:

1.  8 boiling tubes was prepared and each tube were filled with a different amount water and phenol.
2. Then, the tubes  were heated  in a beaker containing water to increased the temperature.
3. The water were stirred and shaken.
4. The temperature for each of the tubes were observed and recorded at which the turbid liquid becomes clear.
5. The tubes were then removed from hot water and allowed for the temperature to reduce gradually.
6. The temperature was recorded at which the liquid become turbid and two layers were separated.
7. Then, the average temperature for each tube at which two phases are no longer seen or at which two phases exist were determined.

RESULT:

Graph of Mutual Solubility Curve of Phenol and Water

QUESTIONS AND ANSWERS:
1. Plot the graphs of phenol composition (horizontal axis) in the different mixtures against temperature at complete miscibility. Determine the critical solution temperatures.

The critical solution temperature 78ºC.


2. Discuss the diagrams with reference to the phase rule.

The graph above in the results shows the graph of temperature at complete miscibility of solution against percentage of phenol composition in the solution. The region outside the curve shows that the solution is in complete miscibility and has only one phase, whereas the region inside the curve indicate the two phase system of the solutions. According to the phase rule,  
F=C-P+2

F is degree of freedom

C is numbers of component

P is number of phase exist
F=2-1+2, thus the degree of freedom for this system is 3. This show that 3 intensive variable must be fixed in order to describe the system completely. As the pressure is fixed, F reduces to 2, and it is necessary to fix both temperature and concentration of phenol in the solution to define the system.


3. Explain the effect of adding foreign substances and show the importance of this effect in pharmacy.

Solubility of a binary system is very important in preparation of drugs in pharmacy. It is very common for two or more liquids to be mixed together in a pharmacy to make a solution, therefore the pharmacist needs to know what liquids can be mixed together without precipitation occurring. The addition of foreign substance to a binary system results in a ternary system. The degree of freedom and miscibility of the two liquid will be affected. If the substance reduces the miscibility of the two liquid, the dispensed medicine may changes its nature and no longer suitable for consumption. Besides, the therapeutic effect of some drug will be reduced and may be harmful to human body. This condition may be arising due to contamination in extemporaneous preparation when the place of medicine preparation is not hygienic. If the substance increases the miscibility of the liquids, the dispensed medicine may be somewhat helpful to the absorption of the drug in the human body.

DISCUSSION:
From the experiment that carried out, we plotted the graph of average temperature versus percentage of phenol. After graph has been plotted, we get an n-shaped-liked graph. The curve shows the limits of temperature and concentration within which the two liquid phases (phenol and water) exist in equilibrium. At the 0% and 100% of phenol, two liquid separations do not occur due to there is no phenol and water molecules respectively of each of the percentage.The region outside the curve contains system having one liquid phase. This means that the phenol and water becomes miscible and exists as one liquid phase at the region outside the curve. Within the region of the curve, there will be existence of two liquid phases. As we add the quantity of phenol gradually, the amount of phenol-rich phase continually increases and the amount of water-rich phase continually decreases. At last, a single phenol-rich liquid phase is formed. The maximum temperature at which the two phase region exists is called the critical solution temperature. The theoretical critical solution temperature in this experiment is 68.0˚C. During this experiment, we are measuring the temperature of the phenol-water system at miscible and temperature at which two phases separated.

From the results that we obtained, the graph is slightly deviated from the theoretical graph. This may be due to some of the errors or mistakes have been occurred during the experiment. First and foremost, when we sealed the tubes, we need to ensure that all the tubes are tightly sealed to prevent evaporation of phenol once the phenol is mix with water. Evaporation of phenol need to be avoided as this may affect the result of this experiment. Besides, when we insert the thermometer into the tubes, we have to make sure that the test tubes are still tightly sealed. If the test tubes are not sealed tightly, the heat will escape to the surrounding when we measured the temperature. This may affect the accuracy of the results. Moreover, we must be careful when we are taking the reading of temperature when heating the mixture and cooling the mixture. This is because the temperature will increase rapidly or drop rapidly. When the turbid liquid in the tubes become clear and homogeneous, we should take the reading immediately. After we left the tubes to cool down, the temperature must be recorded immediately when the liquid become turbid again and form 2 layers. This will help us to get a more accurate reading and plotted a more smoothly graph. Besides, parallax error may occur when measure the volume of components (water and phenol) in the mixture by using measuring cylinder, so the desired volume may not be obtained and this careless mistake may contribute to the inaccuracy of the result. Therefore, pipette is suggested to use during the experiment so that desired volume will be obtained and further contribute to the precise result of critical solution temperature’s value.

CONCLUSION:
The critical solution temperature is 78ºC. The plotting of mutual solubility curve of water-phenol system is achieved.

REFERENCE:

1. Martin's Physical Pharmacy and Pharmaceutics 6th Edition
2. http://www.d.umn.edu/~psiders/courses/chem4643/labinstructions/phenol.pdf
3. http://www.sciencedirect.com/science/article/pii/0378381295968943