Optimization study of combined enteric and time-dependent polymethacrylates as a coating for colon targeted delivery of 5-ASA pellets in rats with ulcerative colitis

Formulation design for colon-specific delivery of 5-aminosalicylic acid (5-ASA) could bring some therapeutic benefits in the treatment of ulcerative colitis (UC).

In the current study, a 3² full factorial design was used to predict optimum coating composed of two enteric (poly methacrylic acid, methyl methacrylates 1:2 and 1:1) and time-dependent (poly ethyl acrylate, methyl methacrylate, trimethylammonio ethyl methacrylate chloride 1:2:0.1) polymethacrylates for colon-specific delivery of 5-ASA pellets. A unique coating composition and coating level predicted by the model was applied onto either inulin-free 5-ASA pellets or inulin-bearing 5-ASA pellets and the coated pellets were examined by dissolution test in-vitro. The coated pellets were also tested in a rat model of UC and compared with the a commercially available colonic delivery system of 5-ASA.

The ratio of the two enteric polymethacrylates and time-dependet polymethacrylate of 16:64:20 w/w at a coating level of 15% was discovered as the optimum coating for delivery of 5-ASA pellets to the colon. In general, the coated pellets offered a better therapeutic outcome compared to commercially available colonic delivery system of 5-ASA and uncoated pellets in terms of colitis activity index and the colon’s tissue enzymes of MDA and GSH.

It seems that the coating composed of enteric and pH-dependent polymethacrylates could tune up the rate of drug release from 5-ASA-coated pellets and trigger drug release based on pH and time.

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Materials: 5-ASA was obtained from Arya pharmaceutical co. (Tehran, Iran). Lactose, Polyvinylpyrrolidone (PVP K30), and Microcrystalline cellulose (Avicel PH-101) were purchased from Darupakhsh (Tehran, Iran). Inulin (catalog # I2255) was purchased from Sigma Aldrich (USA). Eudragit S, Eudragit L, and Eudragit RS were procured from Evonik nutrition and care GmbH (Germany). Potassium dihydrogen phosphate, Sodium hydroxide, Isopropanol, Triethyl citrate,  Butyl alcohol, Acetonitrile, Methanol, Formalin, Trichloroacetic acid, Phosphoric acid, Ellman’s reagent and Thiobarbituric acid were obtained from Merck (Germany). These chemical compounds were of analytical grade. Pentasa (5-ASA controlled-release capsules, 250 mg) were obtained from Shire pharmaceutical company.

Article information: Hossein Shahdadi Sardou, Abbas Akhgari, Amir Hooshang Mohammadpour, Ali Beheshti Namdar, Hossein Kamali, Amir Hossein Jafarian, Hadi Afrasiabi Garekani, Fatemeh Sadeghi, Optimization study of combined enteric and time-dependent polymethacrylates as a coating for colon targeted delivery of 5-ASA pellets in rats with ulcerative colitis, European Journal of Pharmaceutical Sciences, 2021. https://doi.org/10.1016/j.ejps.2021.106072.