Formulation and evaluation of a colon drug delivery system containing diflunisal

Oral drug delivery is the most desirable and preferred method of administering therapeutic agents for providing both systemic and local effects in various parts of the gastrointestinal tract. Recently, greater emphasis has been placed on controlling the site and/or rate of drug release from oral formulations to improve treatment efficacy and patient compliance. Many novel oral drug therapeutic systems have been invented like fast release, targeted release and colon specific drug delivery systems etc... During the last decade there has been an interest in developing site specific formulations for targeting to the colon. The delivery of drugs to the colon has a number of therapeutic implications in the field of drug delivery. Localized delivery of the drugs in the colon is possible only when the drug is protected from the hostile environment of upper GIT. The various approaches that can be exploited to target the release of drug to colon include prodrugs, coating with pH sensitive polymers, coating with biodegradable, timed release systems, osmotic and bioadhesive polymers. In the present study, solid dispersions of pH-dependent, time dependent and combined pH and time-dependent systems were formulated using Eudragit RS100, Eudragit S100, Eudragit L100 and ethylcellulose, with different drug-to-polymer ratios. They were evaluated for their in-vitro release characteristics in an attempt to develop a colon-specific delivery system containing Diflunisal. Release studies of Diflunisal and Diflunisal solid dispersion systems with different polymers were employed using Release apparatus, USP [paddle type] [copley, England] showed that, the combination of pH- and time-dependent systems provided better results than the pH-dependent or the time dependent system alone. Using Eudragit S100 and Eudragit RS100 with Diflunisalin a ratio 2:3:1, respectively for preparing a solid dispersion used for developing a colon-specific delivery system of Diflunisal was the most successful formula. This formula released 0.22 +/- 0.03% of the drug included in it in the stomach pH and 26.29 +/- 0.91% of the drug in the intestine pH and 77.59 +/- 1.79% of the drug in the colon pH

Estimation of paracetamol present in a physical mixture containing ketorolac tromethamine solid dispersion with different polymers

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