AIM: To investigate the release of cyclodextrin-5-aminosalicylic acid (CyD-5-ASA) in cecum and colon.METHODS: An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of alpha-, beta- and gamma-cyclodextrins (CyDs) through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat' s gastrointestinal tract after the oral administration was investigated.RESULTS: The 5-ASA concentration in the rat's stomach and small intestine after the oral administration of CyD-5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-5-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone.CONCLUSION: CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.

In the present study, we compared the systemic exposure of scutellarin following intraportal with intravenous administration to understand the contribution of presystemic hepatic elimination to the low oral bioavailability. Results showed that the hepatic first-pass elimination of scutellarin played an insignificant role in the presystemic elimination of orally administered scutellarin. Moreover, our results suggested that the site of first pass extraction was not the liver, but the gastrointestinal tract.

Objective To explore the absorption characteristics and mechanism of nimodipine for various intestinal segments.Methods The absorption kinetics and absorption site were investigated using in situ perfusion method in rats.The effects of pH value,absorption site and drug concentration on nimodipine absorption were studied.Results Nimodipine has no specific absorption site in rat′s intestine.The absorption rate constants were 0.068 7, 0.062 0, 0.048 9, 0.059 7 h -1 at duodenum,jejunum,ileum and colon,respectively.Conclusions Nimodipine shows absorption behaviour from the whole intestine.The absorption of the drug conforms to the passive transport mechanism and first-order kinetics.The results indicate that nimodipine can be formulated and prepared as sustained-release dosage form.

AIM:To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively.METHODS:DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit L100 and S100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied.RESULTS:Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium, but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets, 5-ASA release was significantly governed by pH. Moreover, the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release.CONCLUSION:Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.

OBJECTIVE To prepare bilayer tablet, which consists of a metoclopramide rapid release layer and a naproxen sodium sustained release layer. METHODS Orthogonal experiment design and central composite design were adopted to optimize the formulation of metoclopramide rapid release layer and naproxen sodium sustained release layer, respectively. The behaviors of compound naproxen sodium sustained release tablets were evaluated by release test in vitro. RESULTS The cumulative release of the bilayer tablet was up to criteria, when the amount of CMS-Na was 30% in metoclopramide rapid release layer, Eudragit~ RLPO and HPMC K4M were 20% and 15% in naproxen sodium sustained release layer. CONCLUSION Orthogonal experiment design and central composite design were successful in optimizing the preparation of tablets with accurate and reliable results.

OBJECTIVE To investigate the relative bioavailability and pharmacokinetics of three ingredients:acetaminophen (A),pseudoephedrine(E) and diphenhydramine(D) between PUBENHUANG tablet and NIKE tablet.METHODS A single oral dose was conducted in six rabbits according to crossover self-control design.The plasma and urine samples were collected and assayed by HPLC method with ultraviolet detection.A C 18 column was used and detected at 256 nm for A,whereas a CN column and detected at 220 nm for E and D.RESULTS These methods exhibited wide linear range for all studied ingredients with extraction recovery ranged from 75% to 105%.Their intra-day and inter-day precision and accuracy were less than 15%.The pharmacokinetic parameters for A in PUBENHUANG tablet and NIKE tablet were t max(0.72±0.44)h and (0.47±0.27)h;c max(26.86±4.63)mg·L -1 and (29.67±7.23) mg·L -1;AUC 0-∞(75.45±14.07)mg·h·L -1 and (71.83±14.62) mg·h·L -1,respectively.The relative bioavailability was (106.4± 15.4)%.X ∞ u for E were (20.50±5.60)mg and (21.04±4.90)mg,X ∞ u for D were (111.01±31.29)μg and (245.11±81.25)μg, respectively.The relative bioavailability for E and D was (96.8±13.7)% and (92.3±12.6)%,respectively.CONCLUSION The bioavailability of A,E and D in two formulations was between 80% and 125% and had no significant difference.