An in Vitro Method to Investigate Food Effects on Drug Release from Film-Coated Beads

Abstract

ABSTRACTThe influence of simulated high-fat meals on drug release from beads coated with modified-release ethylcellulose coating formulations was investigated as a function of plasticizer type and concentration, and coating level. Ethylcellulose-coated beads were soaked in peanut oil prior to testing to simulate the influence of concomitant administration of the dosage form with ingestion of fatty meals. The USP apparatus 3 dissolution procedure was employed to study the drug release properties of the beads. It was found that the ethylcellulose-coated beads plasticized with either triethyl citrate (TEC) or dibutyl sebacate (DBS) had faster drug release rates after the peanut oil treatment. Scanning electron microscopy (SEM) revealed that the peanut oil soak caused the polymeric films to detach from the surface of the bead, producing a series of uneven ridges and cracks in the coating. Modulated differential scanning calorimetry (DSC) demonstrated that the glass transition temperature was increased for DBS-plasticized films soaked in peanut oil, and that it was not influenced for TEC plasticized films. Similar results were found for the puncture strength, percent elongation, and modulus of elasticity for the DBS- and TEC-plasticized films soaked in peanut oil. The results verified that the DBS was solubilized and extracted from the plasticized film during the peanut oil soak, and that the film plasticized with the TEC was not significantly affected by the peanut oil soak. Drug release was influenced by the plasticizer type and concentration, and coating level applied to the beads.