Disintegration tests are performed as per the pharmacopoeial standards. Disintegration is a measure of the quality of the oral dosage form like tablets and capsules. Each of the pharmacopoeia like the USP, BP, IP etc each have their own set of standards and specify disintegration tests of their own. USP, European pharmacopoeia and Japanese pharmacopoeia have been harmonised by the International conference on Harmonisation (ICH) and are interchangeable.
The disintegration test is performed to find out the time it takes for a solid oral dosage form like a tablet or capsule to completely disintegrate. The time of disintegration is a measure of the quality. This is because, for example, if the disintegration time is too high; it means that the tablet is too highly compressed or the capsule shell gelatin is not of pharmacopoeial quality or it may imply several other reasons. And also if the disintegration time is not uniform in a set of samples being analysed, it indicates batch inconsistency and lack of batch uniformity.
The Swiss Pharmacopoeia, way back in 1935, required that a disintegration test should be performed on all tablets and capsules as a criterion of its performance (1). Disintegration test was seen as a test for the uniformity of the compressional characteristics. Optimisation of compression characteristics was done based on disintegration test and the hardness test. Modern medicine era may be considered to be starting from 1937, and from this year tablets became important (2). Tabletting technology was mostly empirical upto the year 1950. Till this year, i.e., 1950, formulators depended on disintegration test, largely, to optimise their compression characteristics. Drug release testing by way of dissolution testing was not much used to characterise the tablets, probably because, by that time, convenient and sensitive chemical analyses were not available before this period.
The British Pharmacopoeia was the first, in 1945, to adopt an official disintegration test. Before 1950, the test became official in USP also. Even at that time, it was recognised that disintegration does not ensure good performance. USP-NF of that period says " disintegration does not imply complete solution of the tablet or even of its active ingredient." In the year 1950, sporadic reports of tablet products of vitamins failing to release their total drug content started appearing. It was only then that formulators realised that though the tablets/capsules showed required disintegration time, they might show poor dissolution, which might effect its clinical performance. Chapman et al., demonstrated that formulations with long disintegration times might not show good bioavailability. Later, John Wagner demonstrated the relationship between poor performance of some drug products in disintegration tests and their failure to release the drug during their gastrointestinal transit. In the 1960s two separate developments occurred. One is the development of sensitive instrumental methods of analysis and the other is the growth of a new generation of pharmaceutical scientists who started applying the principles of physical chemistry to pharmacy. This development was attributed in USA to Takeru Higuchi and his students. In the later period more pharmaceutical scientists like, Campagna, Nelson, and Levy worked on this field and more and more instances of lack of correlation between disintegration time and bioavailability surfaced. It was in the year 1970 that the first dissolution apparatus, the rotating basket was designed and adopted in the USA. An excellent review on disintegration test was written by Wagner in 1971 (3).
Coming to the test, the disintegration test is conducted using the disintegration apparatus. Although there are slight variations in the different pharmacopoeias, the basic construction and the working of the apparatus remains the same. The apparatus consists of a basket made of transparent polyvinyl or other plastic material. It has 6 tubes set into the same basket with equal diameter and a wire mesh made of stainless steel with uniform mesh size is fixed to each of these six tubes. Small metal discs may be used to enable immersion of the dosage form completely. The entire basket-rack assembly is movable by reciprocating motor which is fixed to the apex of the basket-rack assembly. The entire assembly is immersed in a vessel containing the medium in which the disintegration test is to be carried out. The vessel is provided with a thermostat to regulate the temperature of the fluid medium to the desired temperature.
The disintegration test for each dosage form is given in the pharmacopoeia. There are some general tests for typical types of dosage forms. However, the disintegration test prescribed in the individual monograph of a product is to be followed. If the monograph does not specify any specific test, the general test for the specific dosage form may be employed. Some of the types of dosage forms and their disintegration tests are:
1.Uncoated tablets- Tested using distilled water as medium at 37+/-2 C at 29-32 cycles per minute; test is completed after 15 minutes. It is acceptable when there is no palpable core at the end of the cycle (for at least 5 tablets or capsules) and if the mass does not stick to the immersion disc.
2.Coated tablets- the same test procedure is adapted but the time of operation is 30 minutes.
3.Enteric coated/ Gastric resistant tablets- the test is carried out first in distilled water (at room temperature for 5 min.; USP and no distilled water per BP and IP), then it is tested in 0.1 M HCL (upto 2 hours; BP) or Stimulated gastric fluid (1 hour; USP) followed by Phosphate buffer, pH 6.8 (1 hour; BP) or Stimulated intestinal fluid without enzymes (1 hour; USP).
4.Chewable tablets- exempted from disintegration test (BP and IP), 4 hours (USP).
These are a few examples for illustration. The disintegration tests for capsules, both hard and soft gelatin capsules are also performed in a similar manner. Also, the USP also provides disintegration tests for suppositories, pessaries etc.
1.Disintegration test is a simple test which helps in the preformulation stage to the formulator.
2.It helps in the optimisation of manufacturing variables, such as compressional force and dwell time.
3.This test is also a simple in-process control tool to ensure uniformity from batch to batch and among different tablets
4.It is also an important test in the quality control of tablets and hard gelatine capsules.
Advantages of Disintegration tests:
This test is simple in concept and in practice.
It is very useful in preformulation, optimisation and in quality control.
Disintegration test cannot be relied upon for the assurance of bioavailability.
1.The Theory and practice of Industrial Pharmacy by Leon Lachman and Herbert A. Lieberman, CBS Publishers and distributors, New Delhi.
2.Pharmaceutical Dissolution Testing, edited by Jennifer Dressman and Johannes Kramer, Taylor & Francis publications
3.Pharmaceutical Dosage Forms and Drug Delivery Systems by Howard C. Ansel, Loyd V. Allen, Jr.,and Nicholas G.Popovich; Seventh Edition, Lippincott Williams & Wilkins publishers.
1.History of dissolution testing,2000. dissolution Solutions Network, website,
http://www.dissolutionsolutions.net/?page_id=38 (accessed Janary14th, 2010 [Accessed on 24th July 2010]
2.Pharmaceutical Dissolution Testing, by Jennifer Dressman and Johannes Kramer, Taylor & Francis Publications, pages 5,6. [Accessed on 24th July 2010]
3.Wagner J.G.: Biopharmaceutics and relevant Pharmacokinetics, Drug Intelligence Publications, Hamilton, IL, 1971, p.64. [Accessed on 24th July 2010]
4. The Indian pharmacopoeia,1996 [Accessed on 24th July 2010]
5. British pharmacopoeia,2009 [Accessed on 24th July 2010]
6. United States NF, 2008 ( http://www.usp.org/pdf/EN/USPNF/chapter701.pdf ). [Accessed on 24th July 2010]
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