Tuesday, 15 December 2015

PRACTICLE 4

PRACTICLE 4A: Sieving
DATE: 16th November 2015
OBJECTIVES:
1.      To determine the particle size distribution of the powders, lactose and microcrystalline cellulose (MCC)
2.      To determine the different size of particles containing fine and coarse aggregates by sieving.

INTRODUCTION:


Sieving is the method that had been used not only by pharmacists, but also by a chefs, housewives, gardeners and contractors. Sieving is the process of separating the particles or solids substances from a mixture of solids or from the liquid solution which cannot be conducted by hand-picking. This type of particles separating methods is simple in concept, easy to use and is comparatively inexpensive. In ancient times, the Egyptian used sieve to separate grain. But in recent times, sieve are the most commonly used devices for separating the particles according to their respective sizes in the range of 5µm to 125 000µm, which were then are used to determine the distribution of the particle size and this methods also used  to  break  down  agglomerates in the pharmaceutical practices. 
In this practical, we are given two common excipients which are used in tablet formulations named lactose and microcrystalline cellulose (MCC). We are required to use a sieve nest and sieve shaker in order for us to determine the particle size and the particle size distribution for both of the powders.

EXPERIMENTAL METHODS:
Apparatus:
Balance, weighing board, spatula, sieve metal
Chemicals:
Lactose, Microcrystalline cellulose (MCC)
Experimental Procedures:
1.      100 g of MCC was weighed.
2.      The sieve nest was prepared in descending order, the 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 15 minutes.
4.      Upon completion, the powder collected at every sieve was weighed.











RESULTS AND CALCULATIONS:
Diameter (µm)
53
150
200
300
500
Weight (g)
40.3951
3.1585
1.6559
0.0978
0.0000










QUESTIONS

1. What are the average particle size for both lactose and MCC?
 The overall particle size for both lactose and MCC is between 53 µm and 150 µm.
2. What other methods can you use to determine the size of particle?
One of the other methods that be used to determine the particles’ size is by using microscopy. This method can helps in examining each particle individually and distinguish aggregates from the single particles. Coupling to image analysis computers, each fields can be examined hence a distribution can be obtained. Furthermore, sedimentation methods is a method that depends to the velocity of the particle in a fluid. The size distribution of the particle can be determined by examining the suspension of the powder. Next is the coulter counter. This methods is used to measure any particulate materials that are suspended in an electrolyte. When the particles pass through the orifice of the coulter counter, there will be disruptions in the electric impedance which is proportional to the volume diameter and this volume is directly proportional to the volume of the particles. In light scattering method, the particle size distribution is determined by measuring the angular variation in the intensity of the light scattered of a laser beam that pass through a dispersed particulate sample. A bigger size particle will scattered light at small angles while the small particles scattered light at big angles. The size of particles will the can obtained by calculating the volume of equivalent sphere diameter in the Mie Theory.
3. What are the importance of particle size in a pharmaceutical formulation?
In the Noyes-Whitney equation, the dissolution rates is directly proportional to the surface area of the particles, which means that, the smaller the size particles, the bigger the particles’ surface area exposed to the solvent, the higher the rate of dissolution of the solute. Besides, the rate of drying up the solids can also be reduced. This is due to the distance travelled by the moisture particles to reach the surface is decreased. Other than that, the reducing size of particles can helps in increasing the rate of combustion as the area exposed to the air is bigger. In addition, for suspension type of solution, the stability of the active ingredients is important and it is reflected based on the distribution of the particles. A narrow distribution due to the smaller size particles produces more uniform in solution. Based in Stokes’ Law, the smaller the particles size, the lower the velocity of the particles, the higher the stability of the suspensions as the sedimentation of the suspension had been retarded. Last but not least, decreasing in particles’ size helps in increasing the bioavailability of the drug which is in the other words, the ratio of the area calculated for oral route of administration to the intravenous route of administration would be increased.

DISCUSSION:
            In this experiment, we are required to observe the distribution of particle size of lactose and microcrystalline cellulose, MCC. To achieve this requirement, the method used is sieve analysis which is the practice used to assess the particle size distribution of granular materials. Sieve shaker and a set of sieve nest are the main apparatus that were used to conduct this method.  The aperture of the sieve plates that we used had the range of diameter around 53 µm up to 425 53 µm and 53 µm up to 500 µm. The sieve plate with the biggest diameter is placed the upper part of the sieve plate arrangement while the smallest diameter of aperture of the sieve plate would be at the bottom of the arrangement. These sieve nest will be then placed on the sieve shaker. After 15 minutes, each of the powder on each sieve plate are weighed to obtain the distribution of size particles.
            From the experiment conducted, the result shows that most of the lactose particles’ size are in the range between 355 µm up to 25 µm, weighed 61.3789g out of 100g, which is also 61.38% of the total weight. While for the MCC, most of its particles’ size are in the range of less than 53 µm which is 53.6404 and 53.64% of the total weight. These result proves that the particles size of lactose is much smaller and finer than MCC. After each of the powder at each sieve plate are weighed, all the powders are combined and weighed again. Unfortunately, both lactose and MCC total weight before and after the sieving process are not same as 11% of MCC powder is lost but 13.22% excess of lactose is obtained after the experiment.
            This inaccuracy are due to several reasons. Firstly, the sieve nest is not completely cleaned from foreign substances. For example, dust or the residue of the powder left in the sieve plate by the previous group that used the same apparatus. This error could affect the final weight of the lactose. Secondly, the loss some of the powder might due to the incorrect setting up of the sieve shaker or some of the powder might escape to the air due to the air movement when the machine is operating as the powder is light and fluffy. Next, the incorrect method of using the electric balance is also one of the errors that contributes to an inaccurate reading. Other than that, a finer particles are prone to attach to the sieve nest and it is hard to ensure that all of the particle are completely weight. So this would probably decrease the actual weight of the particles of the powder. Last but not least, prolong duration of the sieving process could also lead to an inaccuracy of the results as more of the fine particles are leaks out of the machine and thus decrease the end weight of the powder.
To avoid these errors, ensure that each of the sieve plate are from any dust or residue of the powder. Besides, set up the sieve plates on the sieve shaker and closed the lid tightly to prevent the leaking of powder during the sieving process. In addition, use a brush and shakes the sieve plate slightly to ensure that all of the powder are transferred completely to the weighing boat. Finally, set a constant time taken for each of the experiment to decrease the amount of the powder lost. In conclusion, the particle size of MCC is much more smaller and finer than lactose as most of the MCC particles have sizes around less than 53 µm while for lactose is around 355 µm up to 425µm.

CONCLUSION:
Sieving method is used to determine the size of particles. Each of the particles have different and irregular shapes. The size of particles were also different. Lastly, the errors made in this experiment should be avoided in the future in order to obtain an accurate result.



PRACTICAL 3



PRACTICAL 3A: Phase Diagrams: Determination of Phase Diagram for Ethanol/Toluene/Water System Theory; Three Component Systems

DATE: 2nd November 2015

OBJECTIVES:
1.      To determine the phase diagram for ethanol, toluene and water system.
2.      To determine the solubility limits of water and the two other liquids which are ethanol and toluene, one of which is completely miscible (ethanol) and the other one is partly miscible with water (toluene).
3.      To construct the solubility curve of the system being studied on triangular diagram.
4.      To know the mutual solubility of liquids in a two-phase system by using the triangular coordinates.

INTRODUCTION:
A ternary plot, ternary graph, triangle plot, simplex plot, or de Finetti diagram is a barycentric plot on three variables which sum to a constant. It graphically depicts the ratios of the three variables as positions in an equilateral triangle. Ternary components are represented within the triangular diagram. Any line parallel to a side of the triangular diagram shows constant percentage value for a component.  The concentration of each species is 100% (pure phase) in each corner of the triangle and 0% at the line opposite it. The percentage of a specific species decreases linearly with increasing distance from EACH corners.




In the diagram above, each corner are the pure component. While, each side represents two component mixtures. Any parallel line to a side of the triangle diagram shows constant percentage value for a component. When the line DE which is 20% of A intersect with the line FG which is 50% of B would make an intersection point at K which contained 20% of A, 50% of B and 30% of C.
            Their mutual solubility can be changed when there is an addition of the third component to a pair of miscible liquids. If the third component is more soluble in one of the two different components the mutual solubility of the liquid pair is decreased. But, if it is soluble in both of the liquids, the mutual solubility is increased. However, what will happen to a system like this when it is diluted should also be known and this can be explained through the understanding of the triangular phase diagram.
            Using a ternary plot for depicting compositions has the benefit of that the three variables can be conveniently plotted in two dimensional graph. Using this plot also can create phase diagram by outlining the composition regions on the plot where phases exists. Different composition of the three components are representing on different points on the ternary plot. There are three common methods that can be used to determine the ratios of the three species in the composition. Firstly is the method of estimation based upon the phase diagram grid which is this ternary plotting. Secondly, the methods is for the phase diagrams that do not possess grid lines, the easiest way to determine the composition is to set the altitude of the triangle to 100% and determine the shortest distances from the point of interest to each of the three sides. Last but not least is the method that is based upon a larger number of measurements, but does not require the drawing of perpendicular lines.

EXPERIMENTAL METHODS:
Apparatus:
Balance, weighing board, burette, pipette, conical flask, conical flask stopper, retort stand and clamp, dropper, aluminium foil, filter funnel.
Chemical:
Ethanol, toluene and distilled water.
Experimental Procedures: 
1.  Mixtures of ethanol and toluene are prepared in sealed containers containing percentages of 10%,      25%, 35%, 50%, 65%, 75% and 90% of ethanol.
2.  20mL of mixtures that contained 10% of ethanol are pipetted into a conical flask.
3. The mixture is then titrated with distilled water until cloudiness observed.
4. The solution is shaken well.
5. The volume of distilled water used is measured and recorded.
6. Step 2 to step 5 are repeated by using 20mL of 25%, 35%, 50%, 65%, 75% and 90% of ethanol.
7. The percentage based on the volume of each when the second phase appeared are calculated.
8. Points are plotted on the triangle paper to give a triple phase diagram at the recorded temperature.

RESULTS AND CALCULATIONS:

Before titration

Conical flask
Ethanol
Toluene
%
mL
%
mL
A
10
2
90
18
B
25
5
75
15
C
35
7
65
13
D
50
10
50
10
E
65
13
35
7
F
75
15
25
5
G
90
18
10
2
H
95
19
5
1



After titration

Total volume of mixed solution (mL)
Conical flask
Ethanol
Toluene
Water


%
mL
%
mL
%
mL

A
9.7
2
87.4
18
2.9
0.60
20.60
B
24.2
5
72.5
15
3.4
0.70
20.70
C
33.2
7
61.6
13
5.2
1.10
21.10
D
44.4
10
44.4
10
11.1
2.50
22.50
E
56.5
13
30.4
7
13.4
3.00
23.00
F
61.3
15
20.4
5
17.5
4.45
24.45
G
57.8
18
6.4
2
35.8
11.15
31.15
H
50.1
19
2.6
1
47.2
17.90
37.90



QUESTIONS:
1.      Does the mixture containing 70% ethanol, 20% water and 10% toluene in volume appear clear or does it form two layers?
The mixture appear clear when the mixture are composed of 70% ethanol, 20% water and 10% toluene in volume.

2.      What will happen if you dilute 1 part of the mixture with 4 parts of water, toluene and ethanol?
When 1 part of the mixture is mixed with water or with toluene, two phased-layer are formed or in the other word the mixture is immiscible but 1 one part of the mixture is mixed with ethanol, only one phased-layer is formed which means that the mixture is miscible.


DICUSSION:
A ternary phase diagram is a triangular diagram that shows the phase behaviour of mixture containing three components. By applying the phase rule F = C–P+2 for this experiment, the degrees of freedom in this system is F = 3–1+2 = 4. Degree of freedom of a system is the number of independent variables that does not change the number of phases present at equilibrium. Four degrees of freedom of this experiment are temperature, pressure, and the concentrations of two components, in which the temperature and pressure of the system are constant.
Ethanol acts as surfactant and it causes the water-toluene system become partially miscible. Only a single phase is formed after ethanol is added because all the liquid are miscible. Normal water-toluene system is a two-phase system formed which includes water-rich phase and toluene-rich phase. Water and toluene do not mix thoroughly Toluene is insoluble in water because it is aromatic hydrocarbon that is a non-polar molecule. As the volume of ethanol becomes higher, more volume of water is added to the mixture until cloudiness is observed. This indicates that ethanol increases the miscibility of the water-toluene system and therefore it breaks the homogeneity easily.
Based on the ternary phase diagram plotted, the binomial curve drawn separates the single-phase region and two-phase region. Region bounded by the curve represents two-phase region while region unbound by the curve indicates single-phase region. The region above the curve is region for high ethanol concentration and low toluene concentration. This indicates that solution mixtures that have higher ethanol concentration are more miscible, thus it forms homogenous solution that has only a single-phase solution. For the region below the curve which has lower ethanol concentration, the solution mixtures are less miscible form two-phase solution.   
The curve plotted is nearly perfect except at the intersection point 4. At the intersection point 4, the toluene and ethanol used for experiment are at the same ratio. Different intersection point represents different concentration of the liquids. The total percentage of three components involved in this system adds up to 100% at any intersection point. However, at some intersection point, the total percentage of components in this system is not 100% as the rounding off changes the accurate number. The inaccuracy of phase diagram plotted is due to some errors that occurred during experiment. 
            These are the possible errors that affect the accuracy of data. Parallax error occurs when eyes level of observer is not perpendicular to the reading. Impurities that remain in the apparatus can affect the concentration of liquids. Since ethanol and toluene are volatile, some volume may escape from the solution and this reduces the actual volume of solution. This directly affects the concentration of liquid and volume of water needed for titration.  
            Precautionary steps for this experiment include placing eyes of observer at perpendicular level to the meniscus of liquids. The apparatus must be rinsed properly before using to prevent the presence of impurities. Solution must be mixed well. The conical flask that contains ethanol and toluene should always keep closed as these liquids are easily escaped to the surrounding.  

CONCLUSION:
Water, toluene and ethanol are one of the ternary system that is the phase diagram represented in the form of triangle. Although at first toluene and water form partially miscible liquid and two phase system, single phase was formed after ethanol was added. This is because ethanol acted as a surfactant which increases the miscibility of the water-toluene system and turns it into a single phase system. The higher the concentration of ethanol, the more miscible the mixtures are and this forms homogenous solution consisting single phase solution. Lastly, the errors made in this experiment should be avoided in the future in order to obtain an accurate result.