It is a wise mans part, rather to avoid sickness, than to wishe for medicines. ~Thomas More, Utopia

It is a wise mans part, rather to avoid sickness, than to wishe for medicines. ~Thomas More, Utopia
It is a wise mans part, rather to avoid sickness, than to wishe for medicines. ~Thomas More, Utopia

Tuesday, 24 December 2013

PRACTICAL II : TABLET FRABILITY

TITLE 
Tablet Friability

OBJECTIVE  
To determine the tablet friability using the friability tester at a certain rate within a certain time.

INTRODUCTION
A tablet’s durability may be determined through the use of a friabilator. This apparatus determines the tablet’s friability, or tendency to crumble, by allowing it to roll and fall within the drum. The tablets are weighed before and after a specified number of rotations and any weight loss is determined. Resistance to loss of weight indicates the tablet’s ability to withstand abrasion in handling, packaging, and shipment. A maximum weight loss of not more than 1% generally is considered acceptable for most products. Friability is one of the non official tests. This test is a method to determine physical strength of uncoated tablets upon exposure to mechanical shock and attrition.

APPARATUS AND MATERIALS
 Friability machine
brush

 
10 tablets
weighing boat

EXPERIMENTAL METHOD
10 tablets were selected and weighed. All tablets were put into the drum of the tablet abration and friability tester. The rate of rotation was set to 100 rpm, time to 10 minutes and the operation was started. At the end of the operation, remove all the tablets were removed and ensure it is ensured that all the tablets were free from dust or powder by using the brush. The tablets were then weighted again. The percentage loss of weight was determined. Compressed tablet neither should nor lose more than 1% of its weight.

RESULTS AND CALCULATIONS
Weight of tablet before friability test = 6.5773g
Weight of tablet after friability test = 6.5318g
Weight of tablet loss = 6.5773g – 6.5318g = 0.0455g
Percentage of tablet loss: 0.05455g/6.5773x 100%= 0.6918%

DISCUSSION
Friability is defined as the percentage of weight loss by tablets due to mechanical action during the test. Tablets are weighed after and before the testing and the friability are expressed as the percentage loss. Friability refers to the ability of the compressed tablet to avoid fracture and breaking during transport. This experiment is very important for the transportation of the pharmaceutical product (tablet). An instrument called friabilator is used to evaluate the ability of the tablet to withstand abrasion in packaging, handling and shipping. According to the results, the weight loss of the tablets is not more than 1%. This shows that the test of the friability of the tablet is passed.

CONCLUSION
The results are accepted because the range of friability of the tablet is not more than 1%.

REFERENCES



PRACTICAL I : UNIFORMITY OF DIAMETER, THICKNESS AND HARDNESS

TITLE
Uniformity of diameter, thickness and hardness

OBJECTIVE 
To determine the uniformity of diameter, thickness and hardness of tablets

INTRODUCTION
Tablets and capsules represent unit dosage forms whereas liquid oral dosage forms such as syrups, suspensions, emulsions, solutions and elixirs usually contain one dose of medication in 5 to 30mL. Such doses are erratic by a factor ranging from 20 to 50% when the drug is self administered by the patient. The oral route of drug administration is the most important method for systemic effects. The parenteral route is routinely used in insulin therapy for self-administration of medication. The topical route of administration has only recently been employed with nitro-glycerine for the treatment of angina and scopolamine for motion sickness, but it suffers from effective drug absorption for systemic drug action of drugs that are administered orally, solid oral dosage forms (tablet and capsule) are the preferred class of products of the two forms, the tablet has a number of advantages such as the tablet is an essentially tamper proof dosage form.
Tablets and capsules, like other dosage forms, are subjected to those pharmacopoeial standards which deal with “added substances” with respect to their toxicity, interference with analytical methods and others. However, there are a number of procedures which apply specifically to tablets and capsules, and which are designed, not only to ensure that a tablet or a capsule exerts its full pharmacological actions, but also to determine the uniformity of the physical properties of the official tablet/capsule, irrespective of the manufacturer.
Such standards are found in the British Pharmacopoeia and United Pharmacopoeia and include the uniformity of diameter, uniformity of weight (mass), content of active ingredient, uniformity of content, disintegration and dissolution. Further, there are a number of quality control procedures, which, though widely applied, are not defined by the pharmacopoeias (non-pharmacopoeial standards) such as thickness, hardness and friability.
The following experiments is to demonstrate the application of a number of selected physical and dosage performance tests on samples of commercially available tablets and capsules.

PROCEDURES
  1. 10 tablets selected and uniformity of diameter, thickness and hardness are determined using the Tablet Testing Instrument (PHARMATEST PTB 311).
  2. The deviation of individual unit should not exceed ± 5% for tablets with diameter of less than 12.5mm and ± 3% for diameter of 12.5mm or more.
RESULTS
Tablet
Thickness (mm)
Diameter
(mm)
Hardness
Deviation of diameter (%)
1
5.39
13.16
158.70
0.30
2
5.45
13.11
120.49
0.07
3
5.45
13.12
143.24
0.00
4
5.47
13.12
167.77
0.00
5
5.43
13.11
133.65
0.07
6
5.43
13.11
128.67
0.07
7
5.40
13.10
119.43
0.15
8
5.45
13.12
135.58
0.00
9
5.46
13.11
140.23
0.07
10
5.45
13.10
142.35
0.15
Mean
5.44
13.12
139.01
0.09



DISCUSSION
Tablet thickness is important for tablet packaging; very thick tablets affect packaging either in blisters or plastic containers. The tablet thickness is determined by the diameter of the die, the amount of fill permitted to enter the die and the force or pressure applied during compression.
In general, tablets should be sufficiently hard to resist breaking during normal handling, packaging and shipping, and yet soft enough to disintegrate properly after swallowing. Hardness of the tablet is controlled by (or is affected by) the degree of the pressure applied during the compression stage. Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly intentionally are made hard; others such as immediate-release tablets are made soft.

.In Experiment 1, uniform of diameter was introduced by the British Pharmacopoeia (BP) in 1958 to remove doubt. The test for diameter uniformity is only applied for coated and uncoated tablets. It is not applicable for enteric tablets, film coated tablets and sugar coated tablets. The tolerances for tablet with diameter of 12.55mm or less is ± 5% whereas for diameter of 12.55mm or more is ± 3%. However uniform of thickness and hardness is not required by BP and is also known as non- Pharmacopoeia tests. They are part of a manufacturer’s own product specifications. The tests are carried out to test the strength and resistant force to withstand mechanical shock during handling in production, packaging, distribution and storage. 
The Paralgin tablets are rather hard tablet as the mean of hardness is 139.01.   The diameter is more than 12.55mm and the deviation of individual unit from the mean diameter no exceed ±3%, at most only 0.3%. The mean thickness of the tablets  is 5.44mm.



CONCLUSION
In this experiment, Paralgin tablets have diameter bigger than 12.55mm. Deviation of individual unit from mean diameter of these tablets do not exceed ±3%. Therefore, it is found that all of Paralgin tablets undergoing uniformity test obey the rules and they are all pass the uniformity test.

REFERENCE

http://www.sadgurupublications.com/ContentPaper/2012/4_133_JCCPS_2(1)2012_P.pdf
(http://www.scribd.com/doc/47820668/Quality-Control-Tests-Tablets-Lecture-6)

PRACTICAL V : ANALYSIS OF PARTICLES' SIZE AND SHAPE USING MICROSCOPE

TITLE
Analysis of particles’ size and shape using microscope

OBJECTIVE
1. To analyse the different sizes and shapes of particles under microscope.
2. To describe the distribution of particle size and shape.


INTRODUCTION
Various methods have en used to determine particle sizes and shapes. Microscopic analysis is one of the most simple and widely used method in this case.  It can determine the diameter, shape, and surface area that cannot be determined with the unaided eye.  In this experiment, different sizes and shapes of sands are used. The various sizes of sands used includes 355 µm, 500 µm, 850 µm and lactose. It was observed carefully under the microscope and the observation were drawn at the end of the experiment.
Sand is a naturally occurring granular material composed of finely divided rock and mineral particles.  It exsits in various different sizes ranging from 0.0625 mm (or 1⁄16 mm) to 2 mm.  Fine sand is defined as particles between 0.02 mm and 0.2 mm while course sand as those between 0.2 mm and 2.0 mm. It is used in this experiment as it is inert, easy to obtain and economical. 


METHOD
Materials and Apparatus: Sand particles with size of 355 µm, 500 µm, 850 µm, lactose and a microscope.

PROCEDURE
1. 5 samples of different types of particles are analyzed based on the size and shapes of given particles under the microscope.
2. The samples are examined using the magnification of 4X10 and 10X10.
3. The shapes of particles are observed  and sketched. The overall shape of particles of each powder is described. 



OBSERVATION
355 µm sand
Characteristic: almost same size, small, irregular in shape

4 x 10 magnification                   10 x 10 magnification



500 µm sand
Characteristic: almost same size, larger than 355 µm, irregular in shape

4 x 10 magnification           10 x 10 magnification


                                      
850 µm sand
Characteristic: largest size among all sands, irregular, irregular shape

 4 x 10 magnification             10 x 10 magnification


                          
Various sizes sand
Characteristic: different sizes, irregular shape
4 x 10 magnification             10 x 10 magnification

                                            

Lactose
Characteristic: constant size, very small size, mostly round
4 x 10 magnification             10 x 10 magnification


QUESTIONS
1. Describe the various statistical methods that can be used to measure the diameter of a particle.
There are a few statistical method that can be used in this case, which includes the Feret's diameter (F),  Martin's diameter (M), Projected area diameter (da or dp), perimeter diameter, maximum chord and longest dimension.  Feret's diameter (F) is the distance between two tangents on opposite sides of the particle and parallel to some fixed direction.  While Martin's diameter (M) is the length of the line which bisects the particle image.  The lines may be drawn in any direction which must be maintained constant for all image measurements.  The projected area diameter is the diameter of a circle having the same area as the particle viewed normally to the plane surface on which the particle is at rest in a stable position.  As for perimeter diameter, it is the diameter of a circle having the same circumference as the perimeter of the particle.  For maximum chord, it is a diameter equal to the maximum length of a line parallel to some fixed direction and limited by the contour of the particle.  Lastly, the longest dimension is a measured diameter equal to the maximum value of Feret's diameter.
.

2. Name the best statistical method for every sample that has been used.
Feret’s diameter (F) is the best statistical method for the samples.  This is because the average diameter can be obtained over many orientations nd the mean value can be obtained for each particle diameter.  This in turn produce a more accurate average diameter as the it is taken in more orientations.



DISCUSSION

From the results of observation, it can be seen that there are various sizes and shapes of sands. The sizes of the sands increases from the 355 µm, 500 µm, to 850 µm respectively.  It is also observed that the shapes of the sands are irregular and has some sharp and pointy edges.  On the other hand, the lactose shows that the size of each particle is quite similar and constant.  Lactose also exhibit regular shapes and it is seen mostly to be round and do not have sharp edges.

In this experiment, light microscope is used to observe the sands and lactose for the particle size analysis.  The microscope used is a compound microscope normally used in the laboratory.  Light microscope allows passing visible light to be transmitted through or reflected from the sample through a single or multiple lenses to allow a magnified view of the sample.  The actual power or magnification of a compound optical microscope is the product of the powers of the ocular (eyepiece) and the objective lens. In this practical, we used objective lens of 4x and 10x and eyepiece of 100x.  Therefore, it can give us magnifications of 400 and 1000 respectively.  The observations were then drawn.

As for the analysis of the particle size, Feret’s diameter (F) and Martin’s diameter (M) are among the methods that can be used. In short, Feret's diameter (F) is the distance between two tangents on opposite sides of the particle and parallel to some fixed direction. As for Martin's diameter (M) it is the length of the line which bisects the particle image.  The lines may be drawn in any direction which must be maintained constant for all image measurements.  The longest dimension can also be used as a measurement by equalling to the maximum value of Feret's diameter.


CONCLUSION
There are various sizes for particles like sands. However, lactose exhibit a more constant sizes and shapes.
The particle size analysis can be done with the aid of a light microscope and later determined using Feret’s diameter and Martin’s diameter.


REFERENCE

Physicochemical Principals of Pharmacy (2nd Edition) AT Florence and D.Attwood, The Macmillan Press Ltd.
Pharmaceutics, The science of dosage form design (2nd Edition) Michael E.Alton Edinburgh London New York Philadophia St Louis Sydney Toronto 2002.


PRACTICAL IV : ANGLE OF REPOSE

TITLE
Angle of repose

OBJECTIVE
To evaluate angle of repose of different compositions of sand and factors affecting the angle of repose of materials.  

INTRODUCTION
Angle of repose of powder is important in determining good powder flow. Several methods can be used to measure angle of repose of powder. In this experiment, students are given two different materials with different characteristics, which are taken from dried bulk and mixed with glidant.
           
MATERIALS AND APPARATUS
 1. 100g of sand with particle size of various size, 150µm, 355µm, 500 µm, 850 µm,
2. 10 % Magnesium Stearate.

EXPERIMENTAL PROCEDURES
1.      100g of sand is prepared.
2.      The sand material is poured through a funnel to form a cone.
3.      The tip of the funnel should be held close to the growing cone and slowly raised as the pile grows, to minimize the impact of falling particles.
4.      Stop pouring the material when the pile reached a predetermined height or the base a predetermined width.
5.      Rather than attempt to measure the angle of the resulting cone directly, the height is divided by half the width of the base of the cone.
6.      The inverse tangent of this ratio is the angle of repose.
7.      The experiment is repeated with sand material of different characteristics.

  
RESULTS
 Angle of repose with 1% of glidant
Materials/sand (mm)
Height of the heap without glidant (cm)
Angle of repose without glidant
Height of the heap when added with 5% of magnesium stearate (cm)
Angle of repose with glidant
150
2.2
43.11°
1.7
39.00°
355
2.0
40.40°
2.0
43.60°
500
1.9
38.96°
2.3
47.60°
850
1.8
37.45°
1.9
42.14°
Various sizes
2.3
44.38°
2.9
54.09°

Angle of repose with 5% of glidant
The width of stopper is 2.5 cm.
Materials/sand (mm)
Height of the heap without glidant (cm)
Angle of repose without glidant
Height of the heap when added with 5% of magnesium stearate (cm)
Angle of repose with glidant
150
3.9
57.34°
4.1
58.63°
355
2.2
41.35°
3.5
54.46°
500
1.9
37.23°
2.4
43.83°
850
1.8
35.75°
2.8
48.23°
Various sizes
2.4
43.83°
3.0
50.19°

1.      100g of sand
Particle size of sand
150 µm
355 µm
500 µm
850 µm
Various
Height
4.4 cm
4.2 cm
4.3 cm
4.0 cm
4.0 cm
Half of base width
2.5 cm
2.5 cm
2.5 cm
2.5 cm
2.5 cm
Angle of repose, θ (˚)
θ = tan ̄ ¹ (y/x)
60.40
59.23
59.83
57.99
57.99

90g of sand with 10g of magnesium stearate (10%)
Particle size of sand
150 µm
355 µm
500 µm
850 µm
Various
Height
4.0 cm
2.3 cm
2.2 cm
2.1 cm
2.4 cm
Half of base width
2.5 cm
2.5 cm
2.5 cm
2.5 cm
2.5 cm
Angle of repose, θ (˚)
θ = tan ̄ ¹ (y/x)
57.99
42.61
41.35
40.03
43.83

100g of sands without magnesium stearate:

Materials
Diameter, x(cm)
Height, y(cm)
Angle of repose, θ(˚)  θ = tan ̄ ¹ (y/x)
150µm
2.7
3.2
49.84
355 µm
2.7
2.8
46.04
500 µm
2.7
2.5
42.80
850 µm
2.7
2.3
40.43
Variety of sands
2.7
2.7
45.00

100g of sands with 15% magnesium stearate:


Materials
Diameter, x(cm)
Height, y(cm)
Angle of repose, θ (˚)
θ = tan ̄ ¹ (y/x)
150 µm
2.7
4.1
56.63
355 µm
2.7
3.6
53.13
500 µm
2.7
3.5
52.35
850 µm
2.7
3.3
50.71
Variety of sands
2.7
4.0
55.98


DISCUSSION
There are many factors affecting the angle of repose of a material, which include particle size, individual material, moisture and measurement method of angle of repose.
The individual material will affect the angle of repose, a reflection of the different coefficients of friction between different substances. The size of the particles is a factor. Greater angularity of particles will result in more inter-granular friction and interlocking of particles, contributing to greater shear strength and angle of repose. Other factors being equal, fine grained material will form a shallower pile, with a smaller angle of repose than coarser grains.
Moisture affects the angle of repose, as anyone who has ever built a sand castle can confirm. Water content affects the cohesiveness of particles. If water is added to particles such as sand, water coating the grains would tend to bind them together by its surface tension, giving rise to greater internal cohesion, and therefore shear strength. However, if water is added to completely saturate the pore spaces, the pore water would act as a lubricant between grains and the pore pressure would force the grains apart. Moist sand has a much higher angle of repose than dry sand. Furthermore the method by which the angle of repose is measured can also affect the measurement.
The method used in this experiment to measure angle of repose is called fixed funnel method. However, there are also other methods that can be used to measure the angle of repose of materials
The other methods include tilting box and revolving cylinder method. Tilting Box method is appropriate for fine-grained, non-cohesive materials, with individual particle size less than 10 mm. The material is placed within a box with a transparent side to observe the granular test material. It should initially be level and parallel to the base of the box. The box is slowly tilted at a rate of approximately .3 degrees/second. Tilting is stopped when the material begins to slide in bulk, and the angle of the tilt is measured.
The next method is Revolving Cylinder Method. The material is placed within a cylinder with at least one transparent face. The cylinder is rotated at a fixed speed and the observer watches the material moving within the rotating cylinder. The effect is similar to watching clothes tumble over one another in a slowly rotating clothes dryer. The granular material will assume a certain angle as it flows within the rotating cylinder. This method is recommended for obtaining the dynamic angle of repose, and may vary from the static angle of repose measured by other methods. When describing the angle of repose for a substance, we should always specify the method used.
The glidant added in the experiment is magnesium stearate is used to enhance the flowability of sand mixture. Different concentration of glidant gives different effect on the angle of repose obtained. Generally, powders with angle of repose greater than 50° have unsatisfactory flow whereas powders with angle of repose less than 25° have excellent flow properties.
From the results obtained, there is deviation between the actual angle of repose obtained experimentally with the theoretical value. It showed that some errors had occurred during the experiment. It is suggested that the same person should carry out the experiment from beginning to the end to minimize human error. Furthermore, tapping should be avoided when removing the cylinder to allow the flow of sand. The same measuring method should be utilized throughout the experiment.

CONCLUSION
            The angle of repose depends on the shape, particle size and the cohesive property between particles. The value of the angle of repose will be high if the powder is cohesive and low if the powder is non-cohesive. Glidant added improves flowability of powders thereby decreasing the angle of repose.

REFERENCES
2.      Pharmaceutics, The science of dosage form design (2nd Edition) Michael E.Alton Edinburgh London New York Philadophia St Louis Sydney Toronto  2002.
3.      Physicochemical Principals of Pharmacy (2nd  Edition)
4.      http://en.wikipedia.org/wiki/Angle_of_repose