The influence of ethylcellulose polymers on the physical stability of theophylline pellets coated with Eudragit NE 30 D

The objective of this study was to investigate the influence of ethylcellulose (EC), a high glass transition temperature, non-enteric polymer, on the physical stability and drug release properties of theophylline from pellets coated with the poorly permeable, pH-independent, sustained release coating dispersion, Eudragit NE 30 D. The effect of EC addition on drug release from coated pellets, as well as the physico-mechanical, water vapor permeability, and thermal properties of sprayed films was investigated. The particle size of EC, when mixed in a ratio of 1:1 with the acrylic polymer, affected the drug release rate, with those formulations possessing a smaller particle size exhibiting increased drug release rates. When EC having a mean particle size of 9 μm was present in the acrylic films at a ratio of 1:2, 60% drug was released over 18 h. The drug release rate from these coated theophylline pellets was stable over 3 months at both 25°C/60% RH and 40°C/75% RH when stored in aluminum induction sealed, high density polyethylene (HDPE) containers. Sprayed films stored under the same conditions showed no change in the water vapor permeability and physico-mechanical properties. Modulated differential scanning calorimetry showed three transitions in the composite films, corresponding to the glass transition temperature of Eudragit NE 30 D, ethylcellulose, and a third miscible phase. This third miscible phase was determined to consist of 85% ethylcellulose and 15% acrylic polymer and occupied only a small fraction of the total film.