ABSTRACT
Co-administration of combination of paracetamol with non-steroidal anti-inflammatory drugs showed synergistic effects leading to validation of clinical use of this combination in the treatment of majority of pain conditions. Controlled release drug delivery systems based on ketorolac tromethamine solid dispersion with Eudragit RS100, Eudragit RL100, and ethyl cellulose as polymers in a ratio of [1:3] drug:polymer with paracetamol in a physical mixture form were prepared in order to make use of the synergistic effect of this combination. An accurate simple and precise method was developed for simultaneous determination of ketorolac and paracetamol in the proposed solid dispersion preparation; a derivative spectrophotometric method was utilized. The method is based on measuring the first derivative amplitudes [1]D at 338 and 249 for ketorolac and paracetamol in 0.1 N HCl using 0.1 N HCl as a blank with linearity ranges of 2-10 micro g.ml[-1] and mean percent recovery not less than 99% and S.D not more than 0.03. Similarly, the first derivative values of absorbance [1]D at 304nm and 233 nm were measured for ketorolac and paracetamol respectively in phosphate buffer pH 7.4 using phosphate buffer pH 7.4 as a blank with concentration ranges of 2-10 and 3-10 micro g.ml[-1] for ketorolac and paracetamol respectively. The in-vitro drug release studies were performed for both drugs at different pH values. About 25% of ketorolac tromethamine combined with over 90% paracetamol were released at pH 1.2 whereas over 85% of ketorolac and 99% paracetamol were released at pH 7.4 all over the experimental time period. The obtained results can explain the synergistic effect of the proposed combination as well as the decreased gastrotoxic effects of ketorolac