Comparison of 5-ASA layered or matrix pellets coated with a combination of ethylcellulose and Eudragits L and S in the treatment of ulcerative colitis in rats

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.

2.1. Materials

5-ASA was purchased from Cosar Pharmaceutical Company (Tehran, Iran). Eudragit S and L were kind donations from Evonik (Germany). Ethylcellulose was purchased from ICN (USA). Avicel® PH-102 and polyvinylpyrrolidone (PVP K90) were purchased from Akbarieh (Tehran, Iran). Monobasic potassium phosphate, sodium hydroxide, butanol, methanol, acetonitrile, formalin, isopropyl alcohol, triethyl citrate, thiobarbituric acid, DTNB or Ellman′s reagent, orthophosphoric acid and trichloroacetic acid (TCA) were all purchased from Merck (Germany).

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Hossein Shahdadi Sardou, Fatemeh Sadeghi, Hadi Afrasiabi Garekani, Abbas Akhgari, Amir Hossein Jafarian, Mohammadreza Abbaspour, Ali Nokhodchi, Comparison of 5-ASA layered or matrix pellets coated with a combination of ethylcellulose and Eudragits L and S in the treatment of ulcerative colitis in rats, International Journal of Pharmaceutics, 2023, 122981, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2023.122981.