Practical 4: Particle size analysis (Part B)

Title – Particle Size and Shape Analysis using Microscope

Date : 16 November 2015

Objectives

1)      To analyse and compare the various size and shapes of the prepared samples of 150, 355, 500 and 850 µm and various sizes of sand as well as the sample of lactose and MCC (Microcrystalline Cellulose) under the microscope.

2)      To describe the distribution particle size and shape.

3)      To determine the percentage of different grain sizes contained within a soil.

Introduction

Particle size analysis or dimensions of particulates are important in the field of pharmaceutical science in order to achieve optimum production of efficacious medicine. The particle size and shape analysis are involved in the physical and pharmacological performance of drug, the production of formulated medicines as solid dosage forms and the drugs dissolution in the human body in conjunction with its release properties from the human body. Different particle sizes of powder have different flow and packing properties which alter the volume of powder during each tablet compression event. The particles that have small dimension will tend to increase the rate of dissolution.

As for example, MCC acts as a key diluent for drug formulations and an essential component for almost every kind of oral dosage, including tablets, capsules, sachets, pellets and others, as well. Lactose, the milk sugar is another important excipient which is used to help form tablets due to its excellent compressibility properties. It can used to form a diluent powder for dry-powder inhalations as well. Lactose may be listed as lactose hydrous, lactose anhydrous, lactose monohydrate, or lactose spray-dried.

The particle shape and size can be analysed by many methods. One of it is by using a microscope. This analysis can be used to determine the diameter, shape, and surface area of a particle by dispersing the samples on a microscope slide to avoid analysis of agglomerated particles and looking directly at the particle in a microscopic vision.

The equivalent diameters measured for microscope method are projected area diameter, projected perimeter diameter, Feret’s diameter and Martin’s diameter.

Material

Five different types of sands of 150, 355, 500, 850 µm and various size, as well as powders of MCC and lactose.

Apparatus

Microscope, slide, spatula and weighing boat.

Procedures

1. Seven different types of samples are put on different slides and labelled.

2. The microscope is set up and the first slide sample is observed and examined by 4x10 magnification.

3. The particles shape and size are analysed and sketched.

4. The experiment is repeated using the other particle samples.

Results

Discussion

       After observing and analysing the particles shape, it is found that the overall shape of the particles is irregular or asymmetrical. In order to measure the particle size, the method used is the equivalent diameter, in which the projected area diameter which is measured based on the circle of equivalent area to that of projected image of that particle and the projected perimeter diameter which is based on the circle having the same perimeter as the particle. Both of the diameters are independent of particle orientation. They only consider the two dimensions of the particle, thus it is inaccurate for unsymmetrical particle.

The shapes and sizes of different particles are distinct from each other. All the sand particles have irregular shape with pointed edges but their sizes vary. Meanwhile, the MCC and lactose have granular shape without sharp edges and they are far smaller than even the 150-micron sand particles. When comparing the MCC and lactose, some of the MCC particles are acicular while the lactose particles are more rounded. The particles are dispersed evenly on the slide when doing the microscopy to avoid agglomeration which may affect the observation. The size analysis is carried out on two-dimensional image of particles which are generally assumed to be randomly oriented in 3-dimensional and they are viewed in their most stable orientation.

Feret’s and Martin’s diameter is dependent on both orientation and shape of the particles is another one of the methods to measure the size of particle. These are the statistical diameters which are averaged over many different orientations to produce a mean value for each particle diameter. Feret’s diameter is the mean distance between two parallel tangents to the projected particle perimeter while Martin’s diameter is the mean chord length of the projected particle perimeter, which is the boundary separating equal particles.

Besides, since it is accessing the three-dimensional image of particle, we can use the electron microscope that considering the orientation and shape of the image. Martin's diameter and Feret's diameter of a particle depend on the particle orientation under which the measurement is made. Thus, to obtain a statistically significant measurement for these diameters, a large number of randomly sampled particles which are measured in an arbitrarily fixed orientation is required.

Light microscope method is not suitable for quality control, elaborate sample preparation and slow and rapid operator fatigue. However, the ability to analyse and characterize particle size and shape can significantly improve the manufacturing efficiency and product performance. Thus, we can use of microscopy and image analysis to characterize particle shape, size and volume distribution.

           

There are some precaution steps taken while carrying out the experiment that the students wear goggles and mask all the time to avoid the samples unintendedly get contacted with the eyes. Besides, the experiment is carried out in an open space with a non-windy condition to avoid the sand and powder from distributing everywhere. The careful handling and transferring of the particles from the weighing boat to the slide for microscopy by using spatula is taken into account in order to prevent the particles from mixing with other particles not under study such as dirt and dust and affect the accuracy of result. Next, only small amount of sand and powder is put on the slide and is spread evenly to get a clear image.

Conclusion

We are able to determine the overall distribution of shape and size of this particle that are asymmetrical and irregular. In conclusion, different types of samples have different shape and size analysis. Microscope method is an excellent technique to be used where the light microscope allows the direct observation of the particles in order to analyse the shape and size of particles depending on the presence of agglomeration. The understanding of the characteristic of particularly the active ingredients and excipients as the pharmacologically inactive substance is always being used in the formulation of drugs is thus indeed important.

Questions

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

Various measures of the size of irregular shaped particles as seen under the microscope have been used, chosen according to their theoretical significance or practical ease of measurement.

These include, using Heywood’s notation, which measures the diameter of the particle using projected perimeter diameter, d_p, or projected area diameter, d_a. The projected perimeter diameter is based on a circle having the same perimeter as the particle. The projected area diameter is based on a circle of equivalent area to that of the projected image of a solid particle. Unless the particles are unsymmetrical in three dimensions, then these two diameters will be independent of particle orientation.

Feret’s and Martin’s diameters, where these methods are dependent on both the orientation and the shape of the particles. These are the statistical diameters which are averaged over many different orientations to produce a mean value for each particle diameter. Feret’s diameter refers to the mean distance between two parallel tangents to the projected particle perimeter. Martin’s diameter is the mean chord length of the projected particle perimeter which can be considered as the boundary separating equal particle areas (asymmetry line).

Sieve diameter is defined as the width of the minimum square aperture through which the particle will pass. A common sizing device associated with this definition is a series of sieves with square woven meshes.

The surface diameter, d_s, volume diameter, d_v, and Sauter’s diameter, d32, are defined such that each of them reflects a 3D geometric characteristic of an individual particle. The concept of surface diameter may be mostly used in the field of adsorption and reaction engineering, where the equivalent surface exposure area is important. The volume diameter of a particle may be useful in applications where equivalent volume is of primary interest, such as in the estimation of solids holdup in a fluidized bed or in the calculation of buoyancy forces of the particles. The volume of a particle can be determined by using the weighing method. Sauter’s diameter is widely used in the field of reacting gas-solid flows such as in studies of pulverized coal combustion, where the specific surface area is of most interest.

The dynamic response of a particle in gas-solid flows may be characterized by the settling or terminal velocity at which the drag force balances the gravitational force. The dynamic diameter is thus defined as the diameter of a sphere having the same density and the same terminal velocity as the particle in a fluid of the same density and viscosity.

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

The best statistical method for each of the samples analysed is by Feret’s and Martin’s diameter because both of the parameters give the average diameter over many different orientations to produce a mean value for each particle diameter. This will give an average value which is more accurate.

References

Walton, W. H.   1948.   Feret's Statistical Diameter as a Measure of Particle Size.  nature  162(2.

http://158.110.32.35/CLASS/IMP-CHIM/PGSF21-42.pdf

https://www.horiba.com/fileadmin/uploads/Scientific/eMag/PSA/Guidebook/pdf/PSA_Guidebook.pdf

  

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.

Practical 3: Phase Diagram (Part B)

Part B – Mutual Solubility Curve for Phenol and Water

Date : 2 November 2015

Objectives

1)      To measure the miscibility temperatures of several phenol-water mixtures of known composition.

2)      To determine the critical solution temperature for phenol-water system.

Introduction

Different solutions mix to form different pharmaceutical preparations. Mutual solubility of the components in a liquid-liquid system is terms as miscibility. Complete miscibility is when components mix or dissolve in all proportion at certain temperature while partial miscibility is when there is a formation of layers when certain amount of liquids are mixed, for example, water and ether or phenol and water at certain temperature. Mutual solubility of partially miscible mixture is influenced by temperature. There are systems that having upper critical solution temperature where the mixture of solutions become homogenous as temperature rises, lower critical solution temperature where the mixture of solutions are homogenous at low temperature, and systems having both upper and lower critical solution temperature. In this experiment, phenol and water system is observed, as an example of systems having upper critical solution temperature. They reach a mutual solubility temperature or upper consolute temperature; where the limit of saturation of the composition of the mixture is reached. Above this point, the mixture becomes homogeneous or the liquids become completely miscible. Below this point, the mixture separates into two layers.

The critical solution temperature is the highest temperature that can be reached before two partially miscible liquids become completely miscible. With phase diagram, it is possible to calculate the composition and amount of one phase to the other. The region outside the curve contains a system having one liquid phase and the region below the curve contains a system having two separate phases. This means that phase diagram is a method where the composition of phenol and water can be measured to produce a miscible or partially miscible liquid mixture.

Material 

Phenol, water.

Apparatus

Test tube, parafilm, aluminium foil, thermometer, water bath, test tube holder, measuring cylinder.

Procedures

1.   15 mL mixture of phenol and water are prepared for every test tube.

2.  For mixture containing 10% concentration of phenol, the volume of phenol and water needed to produce 15 mL mixture is calculated and measured using measuring cylinder.

3.   The measured amount of water and phenol are then transferred into a test tube and labelled. The experiment is carried out in the fume hood.

4.   Step 1-3 are repeated to produce mixtures containing phenol concentration scaled between 20%, 50 %, 70 % and 80%.

5.  A thermometer is placed inside each test tube and all of the test tubes are sealed with parafilm and aluminium foil. The test tubes are shaken well before being placed in the water bath.

6.  The temperature at which the liquid becomes turbid and the two layers separate are observed and recorded.

7.   The average temperature is calculated.

8.  The graph of average temperature versus percentage of phenol is then plotted and the critical solution temperature is determined.

Results

Phenol Composition     (%)	Phenol   Volume     (mL)	Water Volume    (mL)	Temperature (°C)
			Clear	Cloudy	Average
10	1.5	13.5	70.0	55.0	62.5
20	3.0	12.0	76.0	60.0	68.0
50	7.5	7.5	80.0	60.0	70.0
70	10.5	4.5	73.0	63.0	68.0
80	12.0	3.0	62.0	50.0	56.0

Discussion

The graph obtained is a phase diagram with two components containing liquid phase condensed system which is used in practice to achieve a single liquid phase product. In this experiment, two different components in liquid phase – phenol and water are used. By plotting the graph of temperature against percentage of phenol in water, a curve is obtained that shows  the limits of temperature and concentration within which two liquid phases exists in equilibrium. A bell-shaped graph is obtained. The region outside the curve shows systems with only one liquid phase whereas the region inside the curve contains systems with two liquid phases. Adding the quantity of phenol gradually increases the amount of phenol-rich phase and decreases the amount of water-rich phase. However, once the concentration of phenol in water exceeds a certain level, a single phenol-rich liquid phase is formed results in complete miscibility between water and phenol, forming homogenous solution. As the temperature raised, the solubility of the component increases. On the other hand, when small amount of water is added to phenol, it dissolves. If the amount of water is increased, the limit of saturation is reached and therefore water forms a separate layer. Phenol is partially miscible with water.

The maximum temperature at which the two phase region exists is called the critical solution temperature. The critical solution temperature in this experiment is 70˚C. During this experiment, the temperature of the phenol-water system at miscible and temperature at which two phases separated is measured. At intermediate compositions and below the critical temperature, mixtures of phenol and water separate into two liquid phases; which is a boundary between homogenous solution that is a single phase and heterogenous solution which is a two phase of the system. A line drawn across the region containing two phases is termed a tie line and it is always parallel to the base line in two-component systems. All systems prepared on the tie line, at equilibrium, will separate into phases at constant temperature. These phases are termed conjugated phases. In the experiment, at temperature 65⁰C, the composition of phenol in water where the mixture starts to become heterogenous is 13% and the composition of phenol in water at the moment the mixture reverts back to homogenous type of solution is 73%. Tie line in a phase diagram is used to calculate the composition of each phase in addition to the weight of the phases.

The upper consolute temperature obtained experimentally is slightly deviated from the theory one. This is due to evaporation of some of the phenol. There are some errors that might have occurred during the experiment. The amount of phenol used may not be exactly accurate and the temperature may not be taken at the exact time when two phases exist or two phases does not exist. However, all the tubes were ensured to be tightly sealed with parafilm and aluminium foil to prevent evaporation of phenol once the phenol is mix with water. The thermometer is placed inside the tubes and sealed together. Therefore, it is important to make sure the test tube is sealed tightly to prevent the heat from escaping to the surrounding when the temperature is measured so that the accuracy of the result can be increase. Besides, the transfer of the phenol into the test tube is carried out in the fume hood to avoid the evaporation of phenol since phenol is highly volatile. Moreover, the reading of temperature during heating and cooling of the mixture is taken carefully. The eyes are ensured to be perpendicular with the meniscus layer of the mercury level in the thermometer to avoid parallax error. A white piece of paper is helpful to be put at the background of the thermometer when taking the reading. When the turbid liquid in the tubes become clear and homogeneous, the reading should be taken immediately. After the tubes were left to cool down, the temperature must be recorded immediately as the liquid become turbid again and form two layers. This will help us to get a more accurate reading and plotted a more smoothly graph. Besides, instrumental error might also occur when the volume of water and phenol by are measured by using measuring cylinder, so the desired volume might not be obtained, contributing to the inaccuracy of the result. Therefore, the pipette is suggested to be use during the experiment so that desired volume will be obtained as well as contributing to the precise result of critical solution temperature’s value. As phenol is a carcinogenic compound, gloves, goggles and mouthpiece was worn all the time during the experiment. Besides, some precautionary steps such as rinsing and cleaning all the glass wares before use is a must to remove the impurities that will contaminate the solution. When heating the tube on the water bath, the temperature of water bath should firstly be ensured that it is not too hot which will later cause the phenol to evaporate easily. The hot tubes were handled carefully using tong or test tube holders instead of using hands to avoid any inconvenient accident.

Questions

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

It is not always necessary to specify the amount of every constituent in order to define the chemical composition of a system. A system consists of phenol and water is one of the whole ranges of systems that exhibit partial miscibility and form two phase liquid-liquid system below critical solution temperature.

This experiment was started by adding 10% w/w of phenol and 70% w/w water. When adding the phenol and water, the mixture initially looked cloudy. This shows that phenol and water are immiscible at room temperature. After that, it was heated in a water bath. During this time, the mixture turned clear. Temperature was taken when the mixture turns clear. At this point, the mixture is said to be miscible. Then the mixture was left to turn cloudy again. When the mixture turned cloudy, the temperature was taken again. At this state, the mixture was in its immiscible state. This has proven that the phases of the mixture will change in different temperature at different composition.

For a system to be in equilibrium, several factors must be considered. The phase rule is a relationship for determining the least number of independent variables that can be changed without changing the equilibrium state of the system as to define the state of the system.

Phase rule is a useful device for relating the effect of the least number of independent variables like temperature, pressure and concentration 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 where P the number of phases that can coexist, C is the number of components making up the phases and F is the degree of freedom. The degree of freedom is dependent on the components of the phases and the phases that coexist. The degree of freedom represents the environmental conditions such as temperature, pressure, concentration, refractive index, chemical composition, and pH. In this experiment, the pressure of the system is maintained. So, the degree of freedom is the temperature and the chemical composition.

Systems for which F = 0 have no degrees of freedom and are said to be invariant. Changing the value of any of the properties that define the state of an invariant system will result in a change in the number of phases present. Systems with one degree of freedom, F = 1, are univariant. For a univariant system, we must fix one variable only to completely define the system.

Applying the phase rule, a two-component condensed system having one liquid phase, whereby phenol and water are miscible with each other at a particular condition, the degree of freedom, F = 2 − 1 + 2 =3. Because the pressure is fixed for this system, F is reduced to 2. We need to fix both temperature and concentration to define this system.

When phenol and water are immiscible with each other, whereby two liquid phases are present, the degree of freedom, F = 2 − 2 + 2 = 2. The two degrees of freedom are temperature and percentage of phenol in water in volume. Then again, the pressure is fixed. We only need the temperature to completely define the system as F is reduced to 1.

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

 Addition of foreign substances to binary system results in ternary system. If the substance is soluble in only one component, or if solubility in both liquids are very different, the mutual solubility decreases because the upper consolute temperature is raised and the lower consolute temperature is lowered. The increase of temperature is due to the salting out of water. Hence, solidification occurs. However, if the substance is soluble in both liquids, the mutual solubility increases as the upper consolute temperature is lowered due to the negative salting out effect, and the lower consolute temperature is raised. This condition is termed as blending.

       Besides having higher or lower critical temperature, the equilibrium curve will also become distorted. The maximum temperature is no longer shown by the system as in which two liquids are present, affecting the degree of freedom and miscibility of the two liquids for drug formulation. Its nature will be no longer suitable for consumption and 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 maybe somewhat helpful to the absorption of the drug in the human body. The elevation or the lowering of the temperature depends not only on the nature and amount of the added substance but also on the composition of the system.

      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 the precipitation. The above effects are important in pharmacy for selection of the best solvent for a drug or a mixture of drugs, overcoming problems that arise during preparation of pharmaceutical solutions and more information about the structure and intermolecular forces of the drug. If solidification occurs at room temperature, pharmacy dispensing error may arise as the dispensed medicines may have some inaccuracies in the percentage of components.

Conclusion

The water-phenol system exists as two phase system in range of 10% to 80% at constant temperature. The critical solution temperature is at 70°C which at any composition of phenol, it will in form of one phase system, where phenol and water miscible completely at this temperature. Above 70°C, phenol and water are miscible, showing the water-rich phase due to high amount of water volume. Below 70°C, the mixture separates into two phases and consequently denotes the phenol-rich phase. To define this system of two phase system, we must fix two variables which are temperature and pressure. When temperature is known definitely the concentration of phenol also determined to duplicate this system.

References

Negi, A. S. & Anand, S. C.   1985.    A Textbook of Physical Chemistry. Wiley Eastern.

Troy, D. B., Remington, J. P. & Beringer, P.   2006.    Remington: The Science and Practice of Pharmacy. Lippincott Williams & Wilkins.