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, MRTs 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.

Key Words:

• colon delivery
• fluorescein
• pressure-controlled release
• time-controlled release
• enteric capsule
• gastric emptying time
• fasted condition
• postprandial condition