PHYSICAL STABILITY TESTING OF DRUGS AND DRUG PRODUCTS

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Tablet Hardness
The “hardness” properties of a tablet are usually  assessed by subjecting the tablets to a diametral failure test. The tablet is  placed  between  two  anvils,  one  of which  is stationary. The other anvil  is  moved at constant speed against the tablet, and the force (as a function of time)  is recorded. The force, at which the tablet breaks is denoted the “hardness” and is usually  measured  in kp (kilopond= kilogram force). Other older units (Strong Cobb Units, SCU, or pound force) are used,  usually when  older instrumentation is  used. Until recently,  one limitation was that forces over 20 kp would  simply  register as F > 20 kp. Newer instrumentation allows for quantitation of higher  forces. From a stability point of  view this is important, since the better a parameter can be quantitated, the clearer the picture that emerges  will be.

For good formulations, this  maximum  does not occur until very  high  pressures (outside the range of pressures  used in pharmaceutical tableting). The maximum  occurs because  above the critical pressure, P*, the tablet will laminate or cap, and a laminated tablet  will contain strata of air and hence  be thicker and weaker. Tablet thicknesses will respond in a manner opposite to the hardness, i.e.,  show a minimum  (e.g., at 500 MPa . The reason for this phenomenon  is the following: As applied  pressure  increases, the number of bonds, N, increases as well. ut assuming that there is a number of bonds, N*, that can be formed, then the strength, H.

Its side from the quoted instance of porosity changes and expansion, there are cases  where crystallization of a soluble compound has occurred via the sorbed amounts of moisture in the tablet, This happens most often with  very  soluble  compounds, and in such  cases it is important  to ascertain storage in a dry environment.

A test that is  now a requirement in the ICH Guidelines  is storage in the final container at 40°C, 75% RH. During this test moisture is  usually adsorbed by the tablets, and this can then cause softening of the binder  bridge  because of moisture uptake. At times,  redrying  will reinstitute the original hardness, Sometimes hardening occurs when the asorbed moisture causes recrystallization of a compound or Sexcipient.

Disintegration
Tablets (whether coated or not) are usually  subjected to a disintegration test. The disintegration was the first in-vitro test used by the U.S.P. It is  now not obligatory compendially (but is  recommended); in an obligatory sense it has been  replaced by the dissolution test. This latter, hence,  is the more important test, but it will be  seen that there often is a correlation between the two, and since the disintegration test is  much more easily carried out, a stability program will  check disintegration frequently, and dissolution less frequently, primarily due to labor intensity. The apparatus used (U.S.P. XX, p.  958)  is  shown  schematically in Fig. 22. It is an apparatus where  six tubes are placed in holders on a circular screen,  which  is then raised and lowered  between 29 and 32 times  per minute through a distance of 5.3-5.7  cm in a 1000 mL beaker containing the disintegration medium (either


 

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