The aim of this study was to evaluate and optimize the combination of time and pH-dependent polymers as a single coating for the design of the colon-specific drug delivery system of 5-aminosalicylic acid (5-ASA) pellets. 5-ASA matrix pellets with a 70% drug load were prepared by the extrusion-spheronization method. The optimal coating formula which included Eudragit S (ES) + Eudragit L (EL) + Ethylcellulose (EC) was predicted for the targeted drug delivery to the colonic area by a 32 factorial design. The ratio of ES:EL:EC and coating level were considered as independent variables while the responses were the release of less than 10% of the drug within 2 h (Y1), the release of 60-70% within 10 h at pH 6.8 (Y2) and lag time of less than 1 h at pH 7.2 (Y3). Also, 5-ASA layered pellets were prepared by the powder layering of 5-ASA on nonpareils (0.4-0.6 mm) in a fluidized bed coater and then coated with the same optimum coating composition. The coated 5-ASA layered or matrix pellets were tested in a rat model of ulcerative colitis (UC) and compared with the commercial form of 5-ASA pellets (Pentasa®). The ratio of ES:EL:EC of 33:52:15 w/w at a coating level of 7% was discovered as the optimum coating for the delivery of 5-ASA matrix pellets to the colon. The coated 5-ASA pellets were spherical with uniform coating as shown by SEM and met all of our release criteria as predicted. In-vivo studies demonstrated that the optimum 5-ASA layered or matrix pellets had superior anti-inflammatory activities than Pentasa® in terms of colitis activity index (CAI), colon damage score (CDS), colon/body weight ratio and colon's tissue enzymes of glutathione (GSH) and malondialdehyde (MDA). The optimum coating formulation showed a high potential for colonic delivery of 5-ASA layered or matrix pellets and triggered drug release based on pH and time.
Keywords: 5-ASA; Colon-specific delivery; Ethylcellulose; Eudragit ulcerative colitis; Pellets.
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