THE EFFECTS OF PH, IONIC CONCENTRATION AND IONIC SPECIES OF DISSOLUTION MEDIA ON THE RELEASE RATES OF QUINIDINE GLUCONATE SUSTAINED-RELEASE DOSAGE FORMS

The dissolution profiles of some extended release quinidine gluconate products were shown to be dependent on several dissolution medium variables. It was shown that, for a quinidine gluconate wax matrix tablet, the dissolution rate has an unexpected inverse relationship to the solubility as a function of pH. The dissolution rate is also affected by the concentration of chloride ion present in the dissolution medium apparently due to the inhibition of disintegration. It was found that the nature of the anion (inorganic vs. organic) of the dissolution buffer plays a significant role in the release of the drug. Salts of inorganic acids used as part of the buffer system lower the rate of release of quinidine gluconate from wax matrix tablets through an inhibition of disintegration. On the other hand, buffer salts of organic acids do not have any appreciable effect on the disintegration or dissolution of these tablets. Since the concentration of chloride ion in both gastric and intestinal juices is approximately 0.1M, this suggests that the use of a dissolution medium containing chloride ion represents the more appropriate approach when an in-vivo/in-vitro correlation is desired. For all the quinidine gluconate controlled release formulations studied, mechanisms of release are of at least two different types. This makes the selection of a single dissolution medium for in-vivo/in-vitro correlations either improbable or impossible.