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

Intestinal absorption and presystemic disposition of sildenafil citrate in the rabbit: evidence for site-dependent absorptive clearance

Sildenafil citrate is the first oral treatment of erectile dysfunction. Its oral bioavailability is about 40%. This research characterized the intestinal transport parameters of sildenafil citrate in rabbit using in situ intestinal perfusion technique. This was studied in flint different anatomical sites, namely duodenum, jejunoileum, ascending-colon and rectum. The results revealed the highest absorptive clearance in the jejunoileum. The value of permeability area product normalized to segment length [ml/min cm] were 0.0101, 0.0063, 0.0059 and 0.0023 and those of percentage absorbed were 67.95, 32.27, 23 and 5.03 in jejunoileum, duodenum, ascending colon, and rectum respectively. The values of the length [cm] required for complete absorption were 87.58, l37.23, 153.27, and 384.09 for each segment in the some order. The absorptive clearance did not correlate with the net water flux in the four anatomical, regions studied, indicating mainly passive diffusion mechanism through transcellular pathway. The plasma sildenafil concentrations achieved dosing intestinal perfusion experiments and sildenafil total body clearance in rabbit were used to calculate the fraction of sildenafil that reached the systemic circulation relative to the amount disappeared from the intestinal segment. Only.34% of sildenafil disappeared from the intestinal segment appeared in the systemic circulation indicating that the presystemic elimination of slidenafil is 66%. These results confirm that the incomplete bioavailability of sildenafil is mainly due presystemic elimination