Pharmaceutical Manufacturing Handbook: Production and

920 PHARMACEUTICAL PREFORMULATION
quality standards according to the monograph of the pharmacopeia. In general,
weight and its variation, content uniformity, thickness, hardness, friability disintegration,
and dissolution should be considered for tablet validation [3] . These factors
must be controlled during tablet production (in - process control) and are validated
after the production to ensure the quality standards.
6.1.5.1 Disintegration
Immediate - release tablets should be readily disintegrated in the stomach when
swallowed. This disintegration involves bursting apart the compact masses by
aqueous fl uid penetrating the fi ne pore structure of tablet. Disintegration testing is
an important part of in - process control testing during production to ensure batch -
to - batch uniformity, but its role in end - product testing has largely been superseded
by dissolution testing because recently modifi ed - release preparations are getting
popular. It was recognized in the 1940s that tablets had to disintegrate in order for
them to be bioavailable due to lack of biopharmaceutical information and primarily
analytical limitations. Later, of course, in the 1950s and 1960s, the pharmaceutical
scientist became aware of the importance of dissolution rates as well.
In general, for the medicinal agent in a tablet to become fully available for
absorption, the tablet must fi rst disintegrate and discharge the drug to body fl uids
for dissolution. The general manner in which a tablet disintegrates is as follows:
(a) the tablet wets down, (b) the dissolution liquid penetrates the pore space, (c)
the disintegrant absorbs water and swells, and (d) this swelling causes the tablet to
break down into granules. Figure 14 shows the disintegration pathways of solid
dosage forms for the dissolution and absorption of drugs. After the disintegration
process, the solid dosage forms change into granules or smaller and fi ne particles
ready for dissolution and absorption in the fl uid.
Solid
dosage form
Dissolution
(major)
Disintegration
Granules
or
aggregates
Dissolution
(major)
Drug in solution
Absorption
Drug in body fluids and tissues
Deaggregation
Primary
drug particles
Dissolution
(major)
FIGURE 14 Disintegration and dissolution pathways of solid dosage forms for absorption
of drug.