Design, Optimization and Evaluation of Chewable Tablets of Clarithromycin using Ion Exchange Resins

Abstract

Ion exchange resins are water-insoluble, cross-linked polymers containing salt forming groups in repeating positions on the polymer chain. Bitter cationic drugs get adsorbed on to weak cationic exchange resins of carboxylic acid functionally like Indion 204, Indion 234 and Tulsion 335 to forms the non-bitter complexes. The present investigation aims at taste masking of bitter clarithromycin using ion exchange resins, which forms complexes, inhibiting its release in saliva. The drug resin complex loading process was optimized for the content of resin, activation, swelling time, stirring time, influence of pH and temperature for maximum drug loading and were subjected to differential scanning calorimetry to confirm the complex formation. These complexes were used to prepare chewable tablets and statistically the taste was evaluated. Acid activated resins comprising of Indion 204, Indion 234 and Tulsion 335 with drug: resin ratio of 1:2, stirred in solution of pH 7-8 at 70o for 6 h had a maximum drug loading and masked the bitter taste of the drug. Differential scanning calorimetry of drug resin complex revealed that there was interaction leading to complex formation. Drug resin complex were formulated into chewable tablet formulations (F1-F9) and evaluated. The various pre-compression and post parameters were found to be within permissible limits. Formulations F3, F6 and F9 containing 1:2 ratios of drug resin complex of Indion 204, Indion 234 and Tulsion 335 revealed maximum taste masking. This was further confirmed by treatment of taste evaluation scores of the volunteers by ANOVA, Dunnet multiple comparison test and Tukey’s multiple comparison test. All the three optimized formulations had a significant difference of P<0.001 when compared to control F10. F6 formulation was widely accepted. Ion exchange complexation could efficiently mask the bitter taste of clarithromycin and achieve palatable taste suitable for pediatric use.