Effect of food intake on the delivery of fluorescein as a model drug in colon delivery capsule after oral administration to beagle dogs

Abstract

The effect of food on the release time of a model drug, fluorescein (FL), has been studied after oral administration to beagle dogs in colon delivery capsule in comparison to conventional gelatin capsule and enteric capsules. The dose of FL was 30 mg for each animal. After oral administration of each test preparation in fasted or postprandial condition (100 grams of commercial solid food was given at 30 min before drug administration), blood samples were collected and plasma FL concentrations were measured spectrofluorometrically. Pharmacokinetic analysis was performed with plasma FL concentration vs. time data and the following parameters were determined; Tmax (the time when plasma FL concentration reaches to its maximum concentration), Cmax (peak plasma FL concentration), Tlag (the time when FL appeared at first into the systemic circulation), AUC (area under the plasma FL concentration vs. Time curve) and MRT (mean residence time). For gelatin capsule, mean Tmax appeared at 0.83 +/- 0.33 (S.E.) h after administration and MRT was 2.67 +/- 0.21 h in fasted condition. By feeding, Tmax and MRT increased to 1.50 +/- 0.76 h and 3.09 +/- 0.49 h. For two enteric HPMCP and Eudragit S capsules, MRT were 2.90 +/- 0.48 h and 5.24 +/- 0.32 h in fasted condition, and 11.30 +/- 1.10 h and 12.83 +/- 0.34 h in postprandial condition, respectively. Tlag also increased by postprandial administration. As colon delivery capsule, time-controlled release capsule (TCC) and two types of intestinal inner pressure-controlled release capsules (PCC) (#1 is a separate type and #2 is a seamless one) were tested. MRT of TCC was 4.76 +/- 0.29 h and 6.43 +/- 0.66 h in fasted and postprandial conditions, respectively. This capsule did not receive the effect of food intake. For #1 PCC, MRTs were 5.32 +/- 0.22 h and 12.28 +/- 0.26 h in fasted and postprandial conditions, respectively. For #2 PCC, MRTs were 5.51 +/- 0.26 h and 13.36 +/- 0.84 h in fasted and postprandial conditions, respectively. In addition, the effect of two times feedings was studied with two PCCs and longer MRTs, 28.44 +/- 1.39 h and 26.32 +/- 1.64 h, were obtained. The release time of FL from PCCs increased by postprandial administration. As compared to the results on two enteric capsules, these PCCs are thought to disintegrate in the colon. However, TCC is thought to disintegrate in the stomach after postprandial administration.

Process, optimization and characterization of mebeverine hydrochloride loaded guar gum microspheres for irritable bowel syndrome

“…For time dependent systems, the location of initial drug release predominantly depends on the transit times of the gastrointestinal tract (GIT). Though the transit time of small intestine is relatively constant (3-4 h) (Davis, Hardy, & Fara, 1986), a large variation in the gastric emptying time was observed which may lead to either a premature release of drug in small intestine or a delayed release far down in the colon (Lee, Wilson, & Mukherji, 2003;Matsuda et al, 1996).…”

In vitroevaluation and pharmacokinetics in dogs of guar gum and Eudragit FS30D-coated colon-targeted pellets of indomethacin

“…For pHsensitive systems, the limited difference in pH between distal intestine and colon sometimes does not allow for reproducible colonic delivery (Ashford et al 1993a,b). And for time-dependent systems, variation in gastric and intestinal transit time may lead to premature drug release in small intestine or delayed release far down the colon (Matsuda et al 1996;Lee et al 2003).…”

Drug delivery to the colon

“…Matsuda et al at the Kyoto University describe the evaluation of both time and pressure-controlled release capsules in dogs and an investigation into the effect of food intake on these devices [20]. The pressure-controlled device used a thin layer of ethylcellulose over a capsule to provide the necessary mechanical strength until the capsule was ruptured by the pressure found in the colon i.e., during stool formation.…”