3.2. Dissolution study of KZ–acid granules
Fig. 3 shows the dissolution profiles of KZ–acid granules prepared
by the wet granulation method. Clearly, the type of organic
acid used has an impact on the extent of dissolution. Compared
to the dissolution rate of KZ without acid, the addition of citric acid
(CA) and tartaric acid (TA) increased the maximum dissolved
amount by approximately 10 times. Although the drug release
gradually diminished, the dissolved amount at 120 min was about
8 times higher than that without any acid. The pH of test medium
was measured after the test and was not changed at 6. Sherif
argued that the pH of the microenvironment is one of the most
effective approaches for enhancing of the solubility of drugs with
pH-dependent solubility (Badawy and Hussain, 2007). It has been
suggested that in order to enhance dissolution rate, the saturation
solubility must increase at solid surface pH, but not the solubility
in the bulk medium, under non-sink conditions. In KZ–acid granules,
the pH-modifying effect of incorporated acids was highly pronounced
at the surface of granules, leading to an enhanced KZ
dissolution rate at the acidified solid surface.
Physical mixtures were prepared using the same compositions
as that of KZ–CA or KZ–TA granules and employed for the dissolution
test. As shown in Fig. 4, the dissolution rate of KZ from the
physical mixture was much lower than that from the wet granule.
Regarding the physical mixture, the incorporated acid was dissolved
immediately in test medium and afterward rapidly diffused