Studies of chitosan/organic acid/Eudragit RS/RL-coated system for colonic delivery.
Prednisolone (PDS) beads were coated sequentially with (i) innermost hydrophobic layer of Eudragit RS/RL, (ii) middle drug release-triggering layer of chitosan, organic acid and Eudragit RS/RL, and (iii) outermost enteric coating layer. Continuous dissolution studies were carried out in artificial gastric fluid (pH 1.2), followed by intestinal fluid (pH 6.8), and finally in colonic fluid (pH 4 and 6) with and without beta-glucosidase. While drug release was prevented in the gastric and small-intestinal fluids, a continuous release was observed in the colonic fluid. Succinic acid provided the fastest rate of release in the colonic fluid compared to citric, tartaric or malic acid. A combined mechanism of drug release is proposed, which considers the swelling of chitosan and Eudragit RS/RL in the presence of succinic acid possibly via electrostatic interaction between the amine groups of chitosan/quaternary ammonium groups of Eudragit RS/RL and the carboxyl groups of succinic acid in aqueous medium. The results of plasma pharmacokinetic studies in Sprague-Dawley rats showed that the developed system provided a significant delay (T(max) 9.3 h) in the absorption profile of PDS compared with simple enteric-coated (T(max) 4 h) or powder (T(max) 1 h) formulation that was taken as proof for the colon-targeted delivery.
Drug Delivery Systems Research Laboratory, College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439, USA.
Karanjit
K
Kaur
Kwonho
K
Kim
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D048271:Chitosan / Q000737:chemistry*; D003106:Colon / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008297:Male; D011108:Polymers / Q000737:chemistry; D011239:Prednisolone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D019802:Succinic Acid / Q000737:chemistry; D013997:Time Factors
D000180:Acrylic Resins; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D005079:Excipients; D011108:Polymers; C050528:Eudragit RS; C058665:Eudragit RL; D048271:Chitosan; D011239:Prednisolone; D019802:Succinic Acid