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NFNF1213 Physicochemical Properties of Drugs

Monday, 15 December 2014

Practical 4b: Sieving

Aim:

To determine the particle size and the size distribution of lactose and microcrystalline cellulose (MCC) by using sieves.


Introduction:

A sieve, or sifter, is a device for separating wanted elements from unwanted material or for characterizing the particle size distribution of a sample, typically using a woven screen such as a mesh or net. The word "sift" derives from 'sieve'. Sieves are commonly used to break down agglomerates, and determine the size and size distribution of a particular powder. Sieve nest is used to determine the particle size and the size distribution of both lactose and microcrystalline cellulose (MCC) which are excipients that commonly used in tablet formulations.




Apparatus / Materials:

Sieve nest
Microscope
Slides
Sands
Electronic balance

Chemicals:

Lactose
Microcrystalline cellulose (MCC)


Procedure:

A.    Determine the particle size and the size distribution by using sieve nest

1.     100g of lactose is weighed by using electronic balance.
2.     The sieve nest is prepared in descending order. Largest diameter on the top and smaller diameter at the bottom.
3.     The lactose powder is placed at the uppermost sieve and the sieving process is allowed to proceed for 20 minutes.
4.     The powder collected at every sieve is weighed upon completion and the particle size distribution is plotted I the form of histogram.
5.     The above procedures are repeated by substitute the lactose powder with Microcrystalline cellulose (MCC)

B.    Particle size and shape analysis using microscope

1.     5 different types of sands, lactose powder and microcrystalline cellulose (MCC) powder is analysed by using microscope.
2.     The size and the shape of the particles are examined.
3.     The particles observed are sketched microscopically.
4.     The general shape for the particular material is determined




Result:

Size of aperture (µm)
Particle size range, x (µm)
MCC
Lactose
Weight (g)
Weight (g)
<53
0<x<53
7.4928
3.7975
53
53<x<150
85.4162
93.7731
150
150<x<200
3.3123
1.4084
200
200<x<300
1.8172
0.8361
300
300<x<425
0.1300
0.0091
425
>425
0.0823
0.0059
Total
98.2508
99.8301



Questions:

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

The average particle size for both lactose and MCC are 50- 150 µm.

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

The other methods that can be used to determine particle size are
a.     microscope methods
b.     coulter counter
c.     laser light scattering method
d.     dynamic light scattering method
e.     sedimentation method

3.     What are the importance of particle size in a pharmaceutical formulation?
Particle size in a pharmaceutical formulation is important in achieving optimum production of efficacious medicines especially in pharmaceutical phase. It also can influence the bioavailability and activity of drug. Particle size may also affect the behaviour of a formulation during processing and, ultimately, its content uniformity. In direct compression tableting, for example, particle size can influence segregation behaviour, 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.

In products where viscosity is important, there is often an optimum particle size distribution (psd) that gives a minimum viscosity whilst maintaining the volume fraction of particles. Of course, the psd will also have a direct influence on the texture and feel of the finished product in terms of both efficacy and consumer perception.


Discussion:

            In this experiment, we observed two materials which are microcrystalline cellulose (MCC) and lactose respectively. We used the sieving method in this experiment. Sieve nest is required so that we are able to determine the particle size and the size distribution of both powders. The sieve nest is arranged in descending order from top to bottom (from largest diameter to smallest diameter). This means, the sieve that have diameter of aperture of 500 µm will be placed at the top followed by 425 µm, 300 µm, 150 µm, and 45 µm. 
            According to the result, most of the MCC fall in the sieve nest which is ranges that less than 150µm. This means that most of the particle size of MCC is smaller than 150 µm. At another experiment, most of the lactose fall in the sieve nest which is ranges that less than 150µm. This means that most of the particle size of lactose is smaller than 150µm. Both MCC and lactose are different materials so they will have different physical properties. In this experiment, MCC has been affected more than lactose during the physical vibration that applied on them because the hardness surface of particle is the one that contribute to the reduction of particle size. The result of this experiment is considered not fully accurate since the weight of the MCC and lactose sum up is not equal to 100g. This is because there are some powders left in the sieves at the end of the experiment. Moreover, small amount of powders spilled out from the container when we moved it from one place to another place. These factors also contribute to the inaccurate results of the experiment.
            So, in order to obtain a more accurate result, we should clean up the sieve to prevent soil particles stuck in the openings which will affect the accuracy of the experiment. Besides, we also have to prepare a suitable size of container to load the powders. If the size of the container is not big enough, powders will spill out. Before we conduct the experiment, we must check the machine whether it is in good condition or not to avoid powders spill out during the physical vibration.


Conclusion:

            In the nut shell, sieving is one of the methods that can used to determine size and particle size distribution of the particles. The distribution of particles size are able to be analysed after conducting this experiment especially in achieving optimum production of efficacious medicines in pharmaceutical phase. Most particles size of lactose is in the range of 50 - 150µm. While as for MCC, most particles size is in the range of 50 - 150µm.In conclusion, lactose has bigger particle size than that of MCC.


References:
  1. www.geog.ucl.ac.uk/about-the.../support...methods/.../sieving-method
  2. http://www.pharma-excipients.com/micro-crystalline-cellulose.html
  3. http://www.pharmaceutical-int.com/article/particle-size-is-important-particle-analysis-techniques.html


Thursday, 11 December 2014

Practical 3b: Determination of Phase Diagram for Ethanol/ Toluene/ Water System Theory Three-Component Systems

Aim: 

1.     To determine the phase diagram for three-component liquid system of Water- Ethanol-Toluene

2.      To determine the solubility limits in a ternary system of water and two other liquids (ethanol and toluene), one of which is completely miscible (ethanol) and the other is partly miscible with water (toluene)

Introduction:

In making pharmaceutical formulation, often multiple components need to be mixed together and need to be in homogeneous form. This is usually possible by knowing the exact ratio of each component to be mixed with regard of some other condition such as temperature. In this experiment, there are three components of concern which were Ethanol, Toluene and Water. If water and toluene mixed together with ethanol, all three components can achieve homogeneous solution at equilibrium if proper proportion was used. Solutions are homogeneous because the ratio of solute to solvent remains the same throughout the solution even if homogenized with multiple sources, and stable because the solute will not settle out after any period of time, and it cannot be removed by a filter or a centrifuge. This type of mixture is very stable, i.e., its particles do not settle, or separate. There are 3 components but only 1 phase exists. Thus, by using the phase rule, we can find out that the degree of freedom is 4 which are temperature, pressure, and concentrations of the two of the three components. A phase diagram is the number of phases of a system that can exist in equilibrium at any time depends on the conditions of temperature, concentration and composition. A phase diagram is a type of chart used to show conditions at which thermodynamically distinct phases can occur at equilibrium.



Each of three corners or apexes of the triangle represent 100% by weight of one component (A, B, or C). As a result, that same apex will represent 0% of the other two components. For example, the top corner point represents 100% B. Each side of the triangle represents a binary mixture where two components mixed together and any line drawn parallel to one of the sides shows the percentage of a particular component. The three lines joining the corner points represent two-component mixture of the three possible combinations of A, B and C. By dividing each line into 100 equal units, the location of a point along the line can be directly related to the percent concentration of one component in a two-component system. The area within the triangle represents all the possible combinations of A, B and C to give three-component system. Line AC , opposite apex B represent system containing A and C (B=0). The horizontal lines running across the triangle parallel to AC denote increasing percentages of B from B=0 (on line AC)to B=100 (at point B). 
Solubility differs when there are different components mixing together. When the third component is added to a pair of miscible liquid, it may affect the mutual solubility. If the third component is more soluble in one of the liquids than in the other, then the miscibility between that pair of liquids decreases. But, if the third component is soluble in both components, then the mutual solubility will increase.

Apparatus:

Burette, pipette, retort stand, conical flask, measuring cylinder, test tube, conical flask stopper

Material:

Toluene, ethanol, distilled water

Procedure:

1.      Mixtures of ethanol and toluene in sealed containers measuring 100cm³was  prepared containing the following percentages of ethanol (in percent): 10,25,35,50,65,75,90 and 95.

2.      20mL of each mixture was prepared by filling a certain volume using a burette (accurately).

3.      Each mixture was titrated with water until cloudiness is observed due to the existence of a second phase.

4.      A little water was added and shakes well after each addition.

5.      The room temperature was measured.

6.      The percentage based on the volume of each component was calculated when the second phase starts to appear/separate.

7.      The points were plotted onto a triangular paper to give a triple phase diagram at the recorded temperature.

8.      A few more measurements had been done if necessary. The determination in the experiment had been done twice.




Result:

% ethanol (v/v)
Volume of Water Used (mL)
Average
Titration I
Titration II
10
1.3
1.1
1.2
25
1.6
1.0
1.3
35
1.1
1.9
1.5
50
1.9
2.1
2.0
65
2.7
2.7
2.7
75
4.3
3.9
4.1
90
10.0
10.4
10.2
95
16.8
14.2
15.5



Calculation:

  Total   
  volume
      Water         
    Toluene 
     Ethanol 
(x+20mL)Volume (mL)%Volume (mL)%Volume (mL)%
21.2
1.2
5.7
18.0
84.9
2.0
9.4
21.3
1.3
6.1
15.0
70.4
5.0
23.5
21.5
1.5
7.0
13.0
60.4
7.0
32.6
22.0
2.0
9.1
10.0
45.45
10.0
45.45
22.7
2.7
11.9
7.0
30.8
13.0
57.3
24.1
4.1
17.0
5.0
20.7
15.0
62.3
30.2
10.2
33.8
2.0
6.6
18.0
59.6
35.5
15.5
43.7
1.0
2.8
19.0
53.5



Questions:

1. Will a mixture containing 70% ethanol, 20% water and 10% toluene remain clear or form two phases?

At these concentrations, the mixture will remain clear and form one liquid phase.

2. What will happen if you dilute 1 part of the mixture with 4 parts of (a) water; (b) toluene; (c) ethanol?


1 part mixture x 20% water = 1 x 20/100 = 0.2 part of water
1 part mixture x 10% toluene = 1 x 10/100 = 0.1 part of toluene
1 part mixture x 70% ethanol = 1 x 70/100 = 0.7 part of ethanol

Therefore, there are 0.7 part of ethanol; 0.2 part of water; 0.1 part of toluene in the mixture.

(a) 1 part of mixture + 4 parts of water:

Water = (0.2+4 / 1+4) x 100% = 84%
Toluene = (0.1 /1+4) x 100% =2%
Ethanol = (0.7/1+4) x 100% =14%

From the phase diagram, this mixture is under the area of the binomial curve. Therefore, a 2 phase is formed.

 (b) 1 part of mixture + 4 parts of toluene:

Water = (0.2 / 1+4) x 100% = 4%
Toluene = (0.1+4 / 1+4) x 100% =82%
 Ethanol = (0.7 / 1+4) x 100% =14%
From the phase diagram, this mixture is outside the area of the binomial curve. Therefore, a clear single liquid phase of solution is formed.

(c)    1 part of mixture + 4 parts of ethanol:

Water = (0.2/ 1+4) x 100% = 4%
Toluene = (0.1 / 1+4) x 100% =2%
Ethanol = (0.7+4 / 1+4) x 100% =94%

From the phase diagram, this mixture is outside the area of the binomial curve. Therefore, a clear single liquid phase of solution is formed.



Discussion:

           A ternary phase diagram has three components. The sum of these subtracted from the total will give the concentration of the third component and because of this in the three-component system, only two concentration term is required to describe the system. In ternary system, which contains three component usually composed of elements as well as included pressure and temperature also. This ternary phase diagram also known as triangular diagram.

          Toluene is soluble in ethanol but in the case of water and toluene, they usually form a two phase system because they are only slightly miscible. However, ethanol is completely miscible with both toluene and water. Thus, the addition of sufficient amount of ethanol to the toluene-water system would produce a single liquid phase as these components were mixed until certain proportion, all the components would be completely miscible and definitely will form homogenous mixture. This experiment is carried out by first making a solution of ethanol and toluene which will be completely miscible and addition of water where at first it will make up two phase. As we continue to add more water until appropriate amount, the mutual solubility of the liquid pair will be increased until at one point, homogenous mixture is formed. The region under the graph shows that there are two phase system form which consist of water and toluene since the solubility of water with toluene is weaker than that with ethanol. Meanwhile the region above the graph shows homogenous mixture.

            From the diagram, each corner represent 100 % of ethanol, 100 % of toluene and 100 % of water while the other two components are 0 %.    The curve of the plotted graph is termed a binodal curve or binodal. The two-phase area is represented by the region bounded by the curve whereas the region of the graph that is not bounded by the binodal curve represents the one–phase region.  Mixture with composition contained within region A are cloudy in appearance due to the phase separation due the amount of ethanol is not sufficient for homogenous mixture to be produced. Mixture with composition that falls into the region of the graph that is not bounded by the binodal curve is clear and homogenous. . For these mixtures, the amount of ethanol is sufficient to produce a single liquid phase. 



A nice and complete binomial curve

           The result obtained were not to the most accuracy as when the data have been plotted it should have look something like the graph shown before this. The line which separate the single-phase system and the two-phase system were the point at which supposed to be obtained through this experiment. There are some errors that were formed when conducting this experiment which lead to this inaccuracy. One of it is the parallax error. Parallax error may occur while taking the reading of the measuring cylinder or the burette. Then, another error that lead to the inaccuracy is the degree of cloudiness is not sure. This is due to the wide range of cloudiness that make exact point when to stop water titration is wrongly determined. As the result, an excess amount or insufficient amount of water is happened which lead to the inaccuracy during conducting the experiment. Besides the volatility of the chemicals also leads to the error. This is because the mixture of toluene and ethanol may vaporize if it is left longer and unsealed. Lastly, the temperature in the laboratory might not constant also affect the system by causing an immiscibility.

         Precautionary steps should be taken while carrying out the experiment to reduce the possibility of error to occur in order to get a better result in this experiment. First of all, the apparatus that want to use should clean and wipe properly and dry before use to prevent the chemicals from being contaminated. Next, it is very important to ensure eye of the observer to be perpendicular to the scale of the measuring cylinder or burette to avoid parallax error as well as the conical flask must be shaken well after every addition of water.  The same observer should be assigned to determine the cloudiness of mixture in order to get a more accurate results. Finally, the mixture of toluene and ethanol should be titrated immediately to prevent vaporization or it should be sealed that can lead to the inaccuracy during conducting the experiment.



Conclusion:

Ethanol,toluene and water system is a ternary system with one pair of partially miscible liquid ( toluene and water). The addition of sufficient amount of ethanol to the toluene-water system would produce a single liquid phase in which all the three components are miscible and the mixture is homogenous. From the experiment, as the number of volume of ethanol by percentage increase and number of volume of toluene by percentage decrease, the volume of water will increase. When the solution is stirred, the transition from one region to another can be observed by appearance (or disappearance) of cloudiness or turbidity in the solution. The turbidity results from scattering of light by the large number of very small “oily” droplets of the second phase that are produced when the system is stirred.



Reference

1.     http://www.chm.davidson.edu/vce/phasechanges/PhaseDiagram.html
2.     Physicochemical Principles of Pharmacy , 3rd edition (1998) . A.T. Florence and D.Attwood. Macmillan Press Ltd.
3.     Physical Pharmacy: Physical Chemistry Principles in Pharmaceutical Sciences, by Martin, A.N.
4.       http://chemwiki.ucdavis.edu/Physical_Chemistry/Physical_Properties_of_Matter/Phase_Transitions/Phase_Diagrams