Monday 30 December 2013

GROUP MEMBER






TENGKU NUR EQHWANA BINTI KU JAYA
A139454


YAP SHI YUN
A139856



SHERON TAPA
A140146


NG KHAI SHIH
A140228


LOH JIA SHIN
A140275


RAUHAH BINTI AB RASHID
A139654

Thursday 26 December 2013

Practical 6: Experiment 1 and 2

Procedures:

Experiment 1: Uniformity of diameter, thickness and hardness
1.      10 tablets were selected and tests for uniformity of diameter, thickness and hardness were tested using the Tablet Testing Instrument (PHARMATEST PTB 311).
2.       The deviation of individual unit from the mean diameter should not exceed ±5% for tablets with diameter of less than 12.5 and ±3% for diameter of 12.5mm or more.
Experiment 2: Tablet friability
1.      10 tablets are selected and weighed.
2.      All tablets are put into the drum of the tablet abrasion and friability tester. The rate of rotation is set to 40 rpm, time to 10 minutes, and the operation is started.
3.      At the end of the operation, all the tablets are removed and the dust or powder is freed using a brush. The tablets are weighed. The percentage loss of weight is determined.
4.      Compressed tablets are not more than 1% of its weight.  

Results and calculations:
Experiment 1

Tablet
Thickness
(mm)
Diameter
(mm)
Deviation

Hardness
1
5.44
13.13
-0.01
150.17
2
5.37
13.12
-0.02
139.87
3
5.46
13.13
 -0.01
145.37
4
5.40
13.19
+0.05
141.29
5
5.51
13.14
 0
132.04
6
5.46
13.11
-0.03
126.89
7
5.44
13.12
-0.02
130.80
8
5.48
13.16
 +0.02
177.90
9
5.38
13.14
 0
137.38
10
5.51
13.10
-0.04
130.09
Average
5.45
13.14

141.18
Average diameter = 13.14mm
13.14mm x 3% =0.39mm
±3% of 13.14mm = 12.75mm - 13.53mm

Experiment 2
Before abrasion
Weight (g)
After abrasion
Weight (g)
Weight loss(g)
Weight loss(%)
6.8170
6.7963
0.0207
0.30

Compressed tablets lost 0.30% of their weight, which is not more than 1% of its weight. Hence, all the 10 tablets have passed the friability test. 


Discussion
One of the pharmacopoeial standards that should be followed by oral dosage forms is the test of uniformity of diameter. Based on the result obtained, the average diameter of tablet is 13.14mm. So, the deviation of individual unit from the mean diameter should not exceed 3% for tablets with diameter of more than 12.5mm. The result shows that all the tablets do not exceed the limit of standard percentage deviation, thus they are all acceptable. For the non-pharmacopoeial standards, we have tests for hardness and thickness of oral dosage forms. The tablet thickness depends on the diameter of the die, the amount of powder permitted to flow into the die and also the force exerted during compression process. Meanwhile, the hardness test measures the strength of pressure required to crush the tablet. Degree of hardness of tablets is determined by the strength of force applied during compression. Tablets should possess sufficient hardness to resist breaking during normal handling, packaging and transporting. At the same time they should also be soft enough to disintergrate after administered orally.
Physical instability in terms of friability is often related to various forces applied on tablets. Friction and shock are the most common forces that cause tablet to break or cap. Transportation and packaging of tablets often exposed tablets to these forces. In this experiment, the rotation of tablets in the tablet abrasion and friability tester subjects them to frictional forces. These frictions result in the tablets to being abraded, hence, loss some materials as well as weight
In this experiment, compressed tablets lost 0.30% of their weight, which is not more than 1% of its weight. Hence, these 10 tablets have passed the friability test. A thick tablet may have tendency to cap whereas thin tablets of large diameter often show extensive capping, thus indicating that tablets with greater thickness have reduced internal stress. (http://www.pharmainfo.net/tablet-evaluation-tests/mechanical-strength-tablets/friability) Hence, the 10 experimental tablets achieve appropriate thickness which gives them a higher friability. 

            Tablets which are too friable may cause undesirable effects, such as inaccurate dose, instability and wastage of money as well as resources. To prevent all these, friability test which is closely related to tablet hardness, is designed to evaluate the ability of the tablet to withstand abrasion in packaging, handling and transportation. During tablet manufacture, friability test should be correlated with actual stress experience. Packaged tablets also should subjected to cross-country shipping tests as well as to various drop tests. 

Tuesday 24 December 2013

practical 6: experiment 4 DOSAGE PERFORMANCE TEST

A) DISINTEGRATION TEST FOR SUGAR COATED TABLETS

MATERIAL AND APPARATUS: Tablet Disintegration Test Apparatus, 3 Ibuprofen tablet and water for disintegration medium.

Method:
The apparatus was set up for disintegration test according to its operation manual and the temperature of disintegration medium was ensured at 37±2°C. The apparatus was set for 60 minutes and then one tablet was added into each tube and was allowed to sink at bottom of tube. Next, before the operation was started the disked was added to each tube. After 60 minutes, the tablet in each tube is checked to know it’s disintegrated or not. If all the tablets disintegrated in 60 minutes that’s means the tablet comply with the test.  Next, if there was any tablet that did not disintegrated, the experiment was repeated using new tablets but the disintegration medium was replaced with 0.1M hydrochloric acid. The tablets were considered comply with the test if all tablets disintegrated in acidic medium.

Results:
All the 3 tablets disintegrate after the test. When the test ended, there still have solid particle in the tube but when we presses the solid particle by using hand it was disintegrate. In this situation the tablet are still considered to pass the disintegration test.

Discussion:
For a drug to be absorbed from a solid dosage form after oral administration, it must first be in solution, and the first important step toward this condition is usually the break-up of the tablet; a process known as disintegration.
The disintegration test determines whether tablets or capsules disintegrate within the prescribed time when placed in a liquid medium in the experimental conditions prescribed above. Disintegration is considered to be achieved when:
a) No residue remains in the tube, or
b) If there is a residue, it consists of a soft mass having no palpably firm, unmoistened core, or
c) Only fragments of coating (tablets) or only fragments of shell (capsules) remain in the tube; if a disc has been used (capsules), fragments of shell may adhere to the lower surface of the disc.
In this experiment, Ibuprofen tablet passes the disintegration test because no residue left after 60 minutes. The possible errors that occur during the experiment are the temperature is less than 37°C so the tablet does not disintegrate according to the body temperature. Other than that, the tablet use has already reached its expiry date and does not disintegrated properly.

Conclusion:
Ibuprofen tablet disintegrated at 37±2°C after 60 minutes.

 B) DISSOLUTION TEST FOR TABLETS

MATERIAL AND APPARATUS: Tablet Dissolution Test Apparatus, 1 tablet of Ibuprofen, 25 ml volumetric flask, syringe and spectrophotometer.

Method:
Firstly, the dissolution vessel was filled up with the buffer solution to 900ml mark and the temperature was set to 37°C. The dissolution medium temperature was ensured at 37±0.5°C. Next, one tablet of Ibuprofen was placed into the dry basket assembly and before start the operation, the stirring speed was set to 150rpm and the basket assembly was then lowered into position in the vessel. The operation was left for 30 minutes and after that, 10 ml of sample was withdrawn from dissolution medium using syringe for analysis. Sampling should be done from a point half away between the surface of dissolution medium and top of rotating basket and not less than 10 mm from the wall of vessel. The volume of aliquot withdrawn was replaced with an equal volume of same dissolution medium.
Next, the standard solution of Ibuprofen was prepared by diluting 10mg of Ibuprofen reference standard to 50 ml with dissolution medium. After that, 2.0ml sample solution and 2.0 ml standard solutions was diluted to 25ml with dissolution medium in separated volumetric flask.  The sample then analyzed for absorbance in 1 cm cell at a wavelength of 221 nm using spectrophotometer.
The percentage amount of ibuprofen dissolved was calculated using the following formula:

 Where:
                At =absorbance of sample solution
                As =absorbance at standard solution
                W =weight of ibuprofen reference standard used
                P =purity of ibuprofen reference standard

The result obtained was determined whether the tablets comply with the requirement of United State Pharmacopoeia.
USP limits: not less than 75% of stated amount of ibuprofen dissolve in 30 minutes.
Result:

ABS
K*ABS
Standard
3.215
3.2148
Sample solution
0.697
0.6969

W=0.01g                P=0.98
So, the percentage amount of ibuprofen dissolved using the formula are:


Discussion:
The release of drug from the tablet into the solution per unit time under standardize condition is called dissolution test. In this experiment, we using USP apparatus I that using basket.
In vitro dissolution testing of solid dosage forms is important because:
Dissolution studies in the early stages of a product’s development allow differentiation between formulations and correlations identified with in vivo bioavailability data. The conduct of such testing from early product development through approval and commercial production ensures control of any variables of materials and processes that could affect dissolution and quality standards. Consistent in vitro dissolution testing ensures bioequivalence from batch to batch. It is a requirement for regulatory approval of marketing for products registered with the FDA and regulatory agencies of other countries.
In this experiment by using the formula, the percentage of ibuprofen dissolve is 23.9%. This amount is does not achieved USP limit that stated that not less than 75% of stated amount of ibuprofen dissolve in 30 minutes. The possible errors that may occur during the experiment are the temperature is less than 37°C so the tablet does not dissolve properly. Other than that, the tablet use has already reached its expiry date and does not dissolve to get it optimum percentage concentration. In order to reduce error, the method of dissolution testing must be controlled to minimize important variables such as basket rotational speed, vibration, and disturbances by sampling probes.
In addition to method of dissolution, formulation and manufacturing controls also play important role why the tablet does not achieved USP dissolution unit. A number of formulation and manufacturing factors can affect the disintegration and dissolution of a tablet, including particle size of the drug substance; solubility and hygroscopicity of the formulation; type and concentration of the disintegrant, binder, and lubricant; manufacturing method, particularly the compactness of the granulation and compression force used in tableting.

Conclusion:
The percentage amount of Ibuprofen dissolve is 23.9%. The dissolution test on Ibuprofen at 37±0.5°C does not reach USP limit that is not less than 75% of Ibuprofen must dissolve in 30 minutes. The method of dissolution, manufacture and formulation play important role in order for tablet to dissolve.

 Question

2. State the type of tablet and capsules that must be tested for uniformity of diameter and uniformity of content.
-uncoated and coated tablet

-suspension in soft capsule

practical 6: experiment 3 Uniformity of weight of tablets and capsules

Title
Uniformity of weight of tablets and capsule

Objective
Determine whether the uniformity of weight of tablets and capsules studied comply with the standard of British Pharmacopoeia or not.

Introduction
            Uniformity of weight of tablets and capsules is an important quality assessment to ensure that each of the tablet and capsule produced meets the requirement of pharmacopoeia standard and also manufacturing standard. Uniformity of weight test is not applicable to tablets and capsules required to comply with the test for uniformity of content. Uniformity of tablets and capsules ensure that patient will get accurate dose of drug in tablet or capsule form to prevent the toxic effect or getting no therapeutic effect. Therefore, uniformity test of weigh of tablets and capsules is carried out in manufacturing process to make sure those produced tablets and capsules fit the requirements.

Apparatus     
Weighing balance, weighing boat

Material        
20 Tablets and 20 capsules

Procedures

Tablets
1)      20 tablets previously selected at random were weighed. The average weight was determined.
2)      The tablets were weighed individually and for each tablet, the percentage deviation of its weight from the average weight was determined.

3)      The deviation of individual weight from the average should not exceed the limits given below:

Average weight of tablet
Deviation (%)
Number of tablets
Less than 80 mg
±10.0
±20.0
Minimum 18
Maximum 2
80-250 mg
±7.5
±15.0
Minimum 18
Maximum 2
More than 250 mg
±5.0
±10.0
Minimum 18
Maximum 2
Capsules
1)      20 capsules were selected at random.
2)      One capsule was weighed. The capsule was opened and the contents were removed as completely as possible. The emptied shells were then weighed. The net weight of its content was determined by subtracting the weight of the shells from the weight of the intact capsule.
3)      The procedure was repeated with other 19 capsules.
4)      The average net weight was determined from the sum of the individual net weights.
5)      The percentage deviation from the average net weight for each capsule was determined. The deviation of individual net weight should not exceed the limits given below:

Average net weight of capsule
Deviation (%)
Number of capsules
Less than 300 mg
±10.0
±20.0
Minimum 18
Maximum 2
300 mg or more
±7.5
±15.0
Minimum 18
Maximum 2

Results and Calculations
Paralgin tablets:

Tablet
Individual weight (g)
Difference between individual weight and average weight (g)
% of deviation
1
0.6376
0.0101
1.48
2
0.7115
0.0278
4.07
3
0.6921
0.0084
1.23
4
0.7057
0.0220
3.22
5
0.7053
0.0216
3.16
6
0.7163
0.0326
4.77
7
0.6636
0.0201
2.94
8
0.6701
0.0136
1.99
9
0.6811
0.0026
0.38
10
0.6810
0.0027
0.39
11
0.6706
0.0131
1.92
12
0.6900
0.0063
0.92
13
0.6745
0.0092
1.35
14
0.6594
0.0243
3.55
15
0.7102
0.0265
3.88
16
0.6992
0.0155
2.27
17
0.7147
0.0310
4.53
18
0.7021
0.0185
2.71
19
0.6583
0.0254
3.72
20
0.6558
0.0279
4.08
i.                    Average weight =   13.6736g  =  0.68368g
                                      20
ii.                  Since the average weight  is 683.68mg which is more than 250mg, so the deviation are ±5% and ±10% ,
a.       % deviation ±5%    =  95% ≤ X ≤ 105%
                   = 649.50 mg ≤ X ≤ 717.86 mg
b.      % deviation ±10%  =  90% ≤ X ≤ 110%
     = 615.31 mg ≤ X ≤ 752.05 mg
iii.                No tablets deviate from the weight so this product passed the uniformity of weight test.


Mefenamic Acid Capsules:

Capsules
Individual weight (g)
Weight of the emptied shells (g)
Net weight of the contents (g)
Difference between individual weight and average weight (g)
% of deviation
1
0.4608
0.0766
0.3842
0.0031
0.80
2
0.4547
0.0733
0.3814
0.0059
1.52
3
0.4528
0.0704
0.3824
0.0049
1.27
4
0.4752
0.0786
0.3966
0.0093
2.40
5
0.4675
0.0710
0.3965
0.0092
2.38
6
0.4610
0.0782
0.3828
0.0045
1.16
7
0.4567
0.0751
0.3816
0.0057
1.47
8
0.4578
0.0732
0.3846
0.0027
0.70
9
0.4690
0.0739
0.3951
0.0078
2.01
10
0.4706
0.0793
0.3913
0.0040
1.03
11
0.4684
0.0756
0.3928
0.0055
1.42
12
0.4094
0.0718
0.3376
0.0497
12.83
13
0.4709
0.0752
0.3957
0.0084
2.17
14
0.4728
0.0826
0.3902
0.0029
0.75
15
0.4680
0.0728
0.3952
0.0079
2.04
16
0.4756
0.0740
0.4016
0.0143
3.70
17
0.4662
0.0716
0.3946
0.0073
1.89
18
0.4620
0.0749
0.3871
0.0002
0.05
19
0.4492
0.0695
0.3797
0.0076
1.96
20
0.4682
0.0732
0.3950
0.0077
1.99

i.                    Average net weight of content = 7.7460 g  =  0.3873 g
                                                              20
ii.                  Since the average weight  is 387.30 mg which is more than 300mg, so the deviation are ±7.5% and ±15% ,
a.       % deviation ±7.5%    =  92.5% ≤ X ≤ 107.5%
                   = 358.25 mg ≤ X ≤ 416.35 mg
b.      % deviation ±15%  =  85% ≤ X ≤ 115%
     = 329.21 mg ≤ X ≤ 445.40mg
iii.                Only one tablet deviates from the weight so this batch of products still considers to pass the uniformity of weight test.



Discussion
          According to the results obtained, the average weight of the tablet Paralgin tablets is  0.68368 g (683.68 mg) which means the range of more than 250 mg is the suitable range chosen from the table of the deviation limits. From the data obtained, it is found that all tablets follow the limits. This shows that almost all tablets tested in this experiment are uniform in the aspect of weight.

 According to the results obtained, the average weight of the capsules is 0.3873 g ( 387.3 mg) which means the range of 300 mg and more is the suitable range chosen from the table of the deviation limits. From the data obtained, it is found that only one capsule has deviation from the weight. This shows that almost all capsules tested in this experiment are uniform in the aspect of weight.

Furthermore, errors might also due to the air flow or wind around the weighing balance to influence the reading of weighing balance. All these errors will lead to inaccuracies of measurement of weight.

The lid of weighing balance should be closed to minimize the error occurred.


Conclusion
The uniformity of weight of tablets and capsules test is useful in quality control during the production of tablets and capsules. In this experiment, it is found that all tablets and capsules used are uniform.

 References
Florence E. Eichie, Ikhuoria M. Arhewoh and Oliver C. Ezeobi, 13 August 2009. In- vitro evaluation of the pharmaceutical quality of some ibuprofen tablets dispensed in Nigeria.
African Journal of Pharmacy and Pharmacology Vol. 3 (10).

Questions:


1    3. Give reasons for the non-compliance to test for uniformity of weight.

The reasons included poor in-process control during manufacturing of tablet and capsule as well as inaccurate weighing and mixing during preparation. During manufacturing, granules may fed unevenly into the die or/ and lower punch moves irregularly which cause variation in capacity of die space, resulting in different weight of tablets or capsules.

4.      Why does dissolution test suitable to be used for batch to batch quality control?

Dissolution test is used to assess the in vivo performance of products. Biopharmaceutical aspects are as important for stability concerns as they are for batch release after production, in vitro dissolution being of high relevance in quality control and quality assurance. In vitro dissolution data will be of great importance when assessing changes in production site, manufacturing process or formulation and assist in decisions concerning the need for bioavailability studies. Thus, dissolution test is suitable to be used for batch to batch quality control.