Manufacture and Quality Control of Tablets
Abstract
A tablet is a solid dosage form that is usually compressed into an oval, circular or square shape. Tablets contain one or more medications that are usually prepared by mould or compression methods. The excipients contained in a tablet are, binders, lubricants and flow aid. The excipients ensure that there is flow and that the tabletting processes is efficient. Quality is necessary during tabletting since tablets are consumed by a human. Several tests are done during tablet manufacturing process to ensure that they are of the required quality. This experiment illustrates the several tests that are performed to ensure that a tablet has met the required minimum specifications before they are allowed to be prescribed or released from the production site.
Results
Visual inspection was the first test to be done for ten tablets. The tablet was inspected for its shape, colour, texture and any physical defects. The directly compressed tablets were found to be circular, had pale pink colour, the texture was rough, and mottling was their physical defect. For granulated tablets, they were also circular, had an orange colour, the texture, however, was smooth and mottling was their physical defect too. Uniformity of mass in the tablet was the second test done on the tablets. The tablets either compressed, or granulated were supposed to have a uniform weight and not more than two tablets were supposed to deviate from the average mass that was calculated. After the calculations, the tablets passed this test with both of them having 0 deviations from the average percentage mass. The graph shows the average weights of the tablets.
Uniformity in diameter is another aspect that was tested. A pair of callipers was used during this test, and the average deviation was also calculated after the diameter of 5 tablets was measured. To pass the test, the tablets were supposed not deviate from the average by 5%. Both tablets passed this test with directly compressed tablets having a percentage of 0.48%, and the granulated tablets had 0.10%.
The graph above gives a clear picture of the results obtained from the measurement of the diameter of varies tablets.
Friability test was also another test that was done. An FR2000 friabilator was used during the exercise. Total of 10 tablets were used during this test. The tablets were weighed then put in the vibrator which was rotated at 25 rpm for 4 minutes. To pass the test, the weight loss of the tablets should not exceed 1.0% for the tablets to have passed the test. The
The graph above represents the results obtained from the friability test. However, both tablets passed the friability test with a percentage loss of 0.48% for granulated tablets and 0.24% for granulated tablets.
Hardness was the last test done on the tablets. 10 tablets were used to carry out this test, and a Holland C50 hardness tester was used to carry out this experiment. To pass this test, each tablet was supposed to have a hardness value of between 30-70N. The tablets had an average hardness of 53.61 for directly compressed tablets and 63.71 for granulated tablets. Two directly compressed tablets were outside the hardness limit while one granulated tablet was also outside the hardness limits. Due to this, the tablets failed the hardness test.
The graph above represents the results obtained from the hardness test.
Discussion
The tablets passed most of the tests except for the hardness test. However according to quality control standards, due to the failure in the hardness test, the drug cannot be released to the public. Visibility tests are important to facilitate packing and to decide which compressing machine is suitable for that particular tablet British Pharmacopoeia Commission, Great Britain. Medicines Commission, General Medical Council (Great Britain). British Pharmacopoeia 2000. Bernan Press (PA); 2000.
. Visibility tests are done to ensure tablets produced are appealing to the patient for them to take the medication. Production of oversized and shapeless tables is not appealing; therefore, patients might not take them. But when a tablet is of the specified shape, thickness and size they look appealing, and patients are most likely to take them. Besides, the tablet should be of desirable colour and odor. Most patients fear yellow drugs due because they are assumed to be bitter. To solve this problem tablets are usually coated.
Uniformity in the mass of the tablets is necessary to be measured routinely to ensure that that the tablet has the proper amount of drug. Failure to monitor this it might lead to compression of tablets that have a high amount the drug that may later lead to overdose when taken by the patients or tablets that have a little drug which if they are taken they will cause therapeutic failure. Throughout the compression process, a sample of 20 tablets should be weighed and their average weights compared to the required standards Aulton ME, Taylor KM, editors. Aulton’s Pharmaceutics E-Book: The Design and Manufacture of Medicines. Elsevier Health Sciences; 2017 Aug 26.
. If they are found to be underweight or overweight necessary adjustments, need to be made for the compression processes to continue.
Uniformity in diameter of the tablets is also another important aspect to consider. The diameter of the tablet shows the thickness of the tablet. Tablet thickness indicated the amount of pressure used during compression of the tablet. The degree of compression pressure not only does it affect the thickness of the tablet but also the hardness Parikh DM, editor. Handbook of pharmaceutical granulation technology. CRC Press; 2016 Apr 19.
. Therefore assessment of tablet thickness during compression is vital to determine the amount of pressure used during compression. Also, the thickness of a tablet is important for counting and packing purposes. Tablet counting using filling equipment uses the thickness of the tablet as a counting mechanism.
Friability test is used to determine the tablets ability to resist fracture or abrasion. The idea behind the test is to implicate some force that is created by sliding and collision of tablets towards each other. This what a tablet goes through during packaging, coating, handling, and shipping. A specific number of tablets are taken, and they are subjected to this kind of force for a specific amount of time in the experiment it was 4 minutes Uddin MS, Mamun AA, Rashid M, Asaduzzaman M. In-process and finished products quality control tests for pharmaceutical capsules according to pharmacopoeias. Br J Pharm Res. 2016;9(2):2.
. The measure of abrasion or friability is expressed as percentage weight loss. For the tablets to have passed the test, they should not have lost not more than 1% of their weight. Moisture content affects the friability of most tablets. A friabilator is the instrument used for this test.
Hardness test determines the amount of force needed to fracture a tablet. Apart from the binders used and the compression pressure during the tabletting process, the hardness of a tablet also depends on the characteristics of the granules that are compressed. Secondly, concentration and the type of lubricant used during granulation. Finally, it also depends on the space between the upper and lower punches of the compressor during the compression time. A hardness tester is used for this test. If a tablet is too hard, it may fail to disintegrate within the required time to deliver its pharmacological effect on the patient, and if the drug is too soft, it may not withstand the packing, handling and shipping operations Aulton ME, Taylor KM, editors. Aulton’s Pharmaceutics E-Book: The Design and Manufacture of Medicines. Elsevier Health Sciences; 2017 Aug 26.
. In the experiment, the hardness test is the only test that has failed so far. Necessary adjustments need to be done so that the tablet meets the required specifications. In this case, the lubricants and binders used during granulation should be assessed. The compression and the space between the compressor punches should be assessed and the relevant adjustments made.
However, not all tests were included in this experiment. Disintegration test is an important test that should be carried out during any tablet compression process. This test measures the amount of time required for a particular percentage of a drug in a tablet to get into solution under a specified condition D’Agostino R. Goodness-of-fit-techniques. Routledge; 2017 Oct 19.
. This test is intended to provide information on the amount of time required for the drugs physiological activity to begin. The test is done by a rotating basket, the flow-through cell and rotating paddle.
In conclusion, quality control is an essential aspect of ensuring that quality drugs are produced throughout the drug production process. Appropriate standards are set by the British pharmacopoeia and the United States Pharmacopeia. The monographs contained in these documents provide appropriate guidelines and standards of the drug manufacturing process.
References
British Pharmacopoeia Commission, Great Britain. Medicines Commission, General Medical Council (Great Britain). British Pharmacopoeia 2000. Bernan Press (PA); 2000.
Aulton ME, Taylor KM, editors. Aulton’s Pharmaceutics E-Book: The Design and Manufacture of Medicines. Elsevier Health Sciences; 2017 Aug 26.
Parikh DM, editor. Handbook of pharmaceutical granulation technology. CRC Press; 2016 Apr 19.
Uddin MS, Mamun AA, Rashid M, Asaduzzaman M. In-process and finished products quality control tests for pharmaceutical capsules according to pharmacopoeias. Br J Pharm Res. 2016;9(2):2.
D’Agostino R. Goodness-of-fit-techniques. Routledge; 2017 Oct 19.