USE OF SPARINGLY SOLUBLE SALTS TO PREPARE ORAL SUSTAINED-RELEASE SUSPENSIONS

The feasibility of preparing oral sustained release suspensions by using sparingly soluble salts of soluble ionic drugs was assessed in this study. Diltiazem was used as a model drug. A less soluble pectate salt of the drug was prepared and encapsulated by a solvent evaporation process. Cellulose acetate butyrate (CAB) was used as the coating polymer. Percent drug release from CAB microcapsules was modified by using hydrophilic polymers and varying microcapsule drug load. The release was independent of pH and ionic strength of the dissolution medium, an advantage over the existing ion-exchange resin approach. The release profiles fitted a bi-exponential equation, suggesting a biphasic release mechanism; an initial burst effect was obtained followed by slow diffusion of drug through the polymeric coat. Suspensions of diltiazem pectate-loaded microcapsules were prepared in a preserved medium containing sorbitol, syrup, and methylcellulose. Redispersibility of suspensions was satisfactory at room temperature and 4 degrees C, but poor at 37 degrees C. The suspended microcapsules resulted in 8-12% increase in drug release after 1 week storage at room temperature compared to dry microcapsules; however, the release did not increase any further upon extended storage. The suspensions were unstable at 37 degrees C, but remained relatively stable at or below room temperature for up to 26 weeks.