PHYSICAL STABILITY TESTING OF DRUGS AND DRUG PRODUCTS
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.
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