Particle size and shape analysis using microscope

TITLE
Particle size and shape analysis using microscope

OBJECTIVES
To determine the size and shape of different types of particles.



PROCEDURES
 1. Using a microscope , 5 different types of sands and powders (MCC, lactose) with particular emphasis on the size and shape of the particles. 

2. The particles observed microscopically is sketched and the general shape for the particular material is determined. The magnification that used are noted in sketching the particles.

RESULTS

QUESTIONS

1. The various statistical method that can be used to measure the diameter of a particle are sieve method which is extremely old technique. The advantage of this method is cheap and readily usable for large particles. But its disadvantage is this method not possible to measure spray and emulsion. The equivalent diameter of this method is equivalent diameter. Second method is microscope method which is the excellent method as it directly look at the particles in question. But this method is not suitable for quality control slow preparation. Next is counter counter method. It is electrical stream sensing zone method which developed by H Coulter to measure any particulate material that can be suspended in an electrolyte and its equivalent diameter is volume diameter. The other method which can be used is laser light scattering method which using a laser diffraction and dynamic light scattering method which involved photon correlation spectroscopy.

2. The best statistical method is a microscopic method as involve the direct with particle in contact with question.

DISCUSSION

   A sieve analysis is a practice or procedure used to assess the particle size distribution of a granular material. Dimension of particulates are important in achieving optimum production of efficacious medicine. Solid particles are often considered to approximate to a sphere and can be characterized by determination of its diameter. Fine particles have irregular and different number of faces and thus, it would be difficult or impractical to determine more than a single dimension. There are various methods in which particle size analysis can be carried out. Among those are, sieve method, microscopic method, coulter counter, laser light scattering method and dynamic light scattering method. The method used in this experiment is the microscopic method.

     The errors that usually occur in a microscopy method are, firstly, the observation varies from person to person due to different types of vision. Secondly, there might be chances of using a wrong magnification during the process of obtaining the results. This is because there are three different magnifications for a light microscope and it totally depends on one’s choice of magnification. Thirdly, the amount of sample placed on the slide can also affect the result of the experiment because if too much of a sample is used, the observation would not be clear and one would be unable to obtain a clear image until an appropriate amount of sample is used.

    There are a few steps that should be taken to overcome the errors mentioned above. For example, only one person should observe the image under the microscope and draw the image obtained to prevent variation in observations of one sample.  Next, to overcome the probability of using a wrong magnification, one should always start observing a sample under a magnification of 10, followed by 40, and then 100. Other than that, one should be aware that too much amount of a sample cannot be placed on the slide because as mentioned above, this might affect the results obtained. Thus, a fair amount of sample should be placed on the slide for each observation.

CONCLUSION

 Microscope method is one of the methods that can be used for particle size analysis, but, just like any other method, there will always be advantages and disadvantages for this method as well. This method can be said to be an excellent technique because it involves direct vision at the particles in question. The advantages include, it is relatively cheap and the disadvantages are, it is not suitable for quality control and the operator variability on the same sample is present.

 

Sieving

TITLE
Sieving

OBJECTIVES
1. To detrmine the particle size of solid lactose and microcrystalline cellulose (MCC) by using sieve nest
2. To odentify the particle size distribution of a particular powder.

INTRODUCTION

Sieve is an essential part of every pharmaceutical production process, particularly as product quality and integrity are so important. The use of a sieve gets rid of oversized contamination to ensure that ingredients and finished products are quality assured during production and before use or despatch. In basic terms, a sieve consists of a housing containing a removable wire mesh of a defined aperture size. This assembly is vibrated by an electric motor so that small particles can pass through the mesh apertures and any particles or contaminations that are too big remain on the top. Most units used in the pharmaceutical industry tend to be circular and of a high-quality good manufacturing practice (GMP) design by ensuring accurate separation. Stainless steel mesh with a high tolerance on the apertures is also specified to give excellent product quality

.

In this experinment, student are given two common excipient used in tablet formulations, namely Lactose anfd Microcrystallipe (MCC). The objectives of the experinment is to determine the particle size and the size distribution of both powder.

MATERIALS

Lactose, Microcrystalline Cellulose (MCC)

APPARATUS

Sieve nest, weighting boat, and spatula

PROCEDURE

1. Firstly, 100 g of Microcrystalline Cellulose (MCC) is weighing.

2. The sieve nest was prepared and arranged in descending diameter to the smallest, from top a bottom.

3. The Microcrystalline Cellulose (MCC) was placed at the uppermost sieve and the sieving process in 10 minutes.

4.  Next, the Microcrystalline Cellulose (MCC) collected at every sieve was weighed and the particle are distribution was plotted in the form of histogram

5. Step 1-4 was repeated by using Lactose

RESULT

Size (diameter), μm	Particle size range, μm	MCC
		Weigh (g)	Frequency (%)
<50	0 ≤x <50	2.8780	2.88
50	50 ≤x <150	91.2385	91.24
150	150 ≤x <300	4.4295	4.43
300	300 ≤x <425	0.1026	0.10
425	425 ≤x <500	0.0022	2.20 x 10-3
500	500 ≥	0.0009	0.90 x 10-3

Size (diameter), μm	Particle size range, μm	Lactose
		Weigh (g)	Frequency (%)
<45	0 ≤x <45	0.2537	0.26
45	45 ≤x <150	4.5063	4.54
150	150 ≤x <300	26.5859	26.81
300	300 ≤x <425	67.7878	68.35
425	425 ≤x <500	0.0046	4.64 x 10-3
500	500 ≥	0.0392	0.040

QUESTIONS

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

The average particle size of lactose is between the ranges of 32 µm to 400 µm. The average particle size of microcrystalline cellulose (MCC) is average particle size 50µm.

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

Laser diffraction is another method that can be used to determine the size of particles for the duo.  For the measurement the powder is passing a laser beam. The light of the laser beam is diffracted in different directions and the scatter pattern is recorded by detectors. The scatter pattern is strongly related to the particle size and the size distribution of the particles.

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

Conventional solid dosage forms such as tablets are administered orally for local and systemic action. The local activity (acid neutralizing capacity) attributed by antacid formulations is proportional to the particle size of the ingredient. Particle size is having a pronounced effect on the absorption of drugs with low aqueous solubility. This was demonstrated with tablets, capsules, suspensions and suppository dosage forms. Particle size of the pharmaceutical semi-solid dosage forms influences the efficacy, safety and performance of the dosage form. It affects skin penetration and can also influence the flux rate of the active ingredient. In addition, particle size is a key factor in determining process ability, spread ability and the rheological behaviour of a formulation

References:

http://www.pharmainfo.net/tegkmurthy/blog/influence-particle-size

Phase diagrams : Mutual solubility curve for phenol and water

Title

Phase diagrams : Mutual solubility curve for phenol and water

Objectives

1.      To determine the critical point for phenol and water.

2.  To know the miscibility temperatures for water and phenol.

Introduction

A few liquids are miscible with each other in all proportions such as ethanol and water. Others have miscibility in limited proportion in other liquids such as etherwater. When the temperature reached the critical solution temperature or consolate point is attained, and above this point the liquids are completely miscible. 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. Presence of a third component usually affect the mutual solubility for a pair of partially miscible liquids.

Procedures

    1. Mixtures of phenol and water is prepared in five tightly sealed tubes containing amount of phenol      between 8% to 80%.

    2.  All the tubes then heated in a beaker containing water.

    3. The water were stirred and shaked the tubes as well.

   4.  The temperature were observed and recorded at which the turbid liquid become clear.

    5.  The tubes then removed from the hot water and recorded the temperature when the liquid become    turbid and two layers are separated.

   6.  Lastly the average temperature for each tube at which the two phases are no longer seen or at which two phases exist were recorded.

Results

Phenol composition (% by weight)	Phenol volume (mL)	Water volume (mL)	Single phase (oC)	Two phase (oC)
8	1.6	18.4	59	46
20	4.0	16.0	74	64
40	8.0	12.0	79	70
60	12.0	8.0	65	-
80	16.0	4.0	55	-

 Questions

1       Graph:

The critical solution temperature is 80 ^oC.

2    2.   The graph shows the temperature at complete miscibility against percentage by weight of phenol in water. Phase rule is a useful device for relating the effect of the least number of independent variables upon the various phases that can exist in an equilibrium system containing a given number of components. Phase rule is expressed as F = C – P + 2 in which F is the number of degree of freedom in the system, C is the number of components and P is the number of phases present. In the region inside the curve has two liquid phases while the region outside the curve has single liquid phase. In this experiment, we have two components which is phenol and water (C). The phase (P) will be depends on the condition whether phenol and water are miscible or phenol and water are immiscible. If they are miscible, so the P will be 1 and if they are immiscible the P will be 2. Therefore, to find the number of degree of freedom in the system:

If phenol and water are miscible,

F = C - P + 2

   = 2 – 1 + 2

   = 3

If phenol and water are immiscible,

F = C – P + 2

   = 2 – 2 + 2

   = 2

Since pressure is fixed in this system, so the F for if phenol and water are miscible is reduced to 2 and the F if phenol and water are immiscible is reduced to 1. Therefore to define the system, we only need to know the concentration and temperature for if phenol and water miscible and we need to know the temperature only for if phenol and water immiscible.

1    3.  Adding a foreign substance may change the system of the mixture. In this case, the experiment involves only a binary system. If both the solutions are immiscible, adding a foreign substance (either solid or liquid) to the mixture forms a partition solution where the substance will distribute itself between the two phases. This happens to water and a liquid hydrocarbon. In another case, where a mixture contains two liquids. When a foreign substance is added, the mutual solubility will increase if and only if the foreign substance is soluble in both the liquids. This is also called blending. In the final case, as similar to the one before; where a foreign material is added into a mixture containing 2 liquids. But now the foreign substance is only soluble in one of the liquid. This decreases the mutual solubility. In pharmaceuticals, it is useful to apply the concept of blending. Where it is necessary to increase the mutual solubility of the medicines (involving a binary system that is not very miscible). For example for manufacturing cream by adding a surfactant to an oil and water mixture to keep them in their agitated phase.

 Discussion

There were several errors committed in the experiment which had reduced the accuracy of the results. For instance, parallax errors would have occurred during the procedure of pipetting the phenol into the tubes. Although this does not seem to be relatively a serious blunder. But for the extremities of the scale which are 8% and 80% phenol concentrations, it does cause a defect to the results obtained. The eyes were not placed perpendicular to the scale of the pipette.

Besides, one of the predominant factor which we feel had cause most of the imperfection was not giving enough shake or insufficient stirring to the mixture. This had led to the mixtures being slightly cloudy and in worst case, one or two tubes had no visible turbid. Thus, we felt that recording the temperature was to no avail. Thus, we resort to comparing our reading with the other groups and ameliorated our results since we were devoid of time to repeat the experiment. 

We were away from our responsibility of constantly keeping an eye on the tubes that were being heated. All of us were quite lethargic and fed up of wearing the breath limiting mask and the tight gloves despite knowing the safety benefits. Thus, we did not know the exact temperature for the vanishing of the turbid.

Conclusion

The critical point for phenol and water is 80 ^oC. The miscibility temperature for water and phenol are the region out the curve which are different for all five tubes because of different composition of water and phenol in each tube.

References

      1.    Physicochemical Principles of Pharmacy,   3^rd edition   (1998). A.t. Florence and D.Attwood.      Macmillan Press Ltd

      2.  Physical Pharmacy: Physical Chemistry Principles in Pharmaceutical Sciences, by Martin, A.N.