This study was designed to develop matrix type of transdermal-controlled delivery system for zidovudine using Eudragit L100 by varying the amounts of drug in addition to polyethylene glycol as a plasticizer and Tween 80 (R) as a penetration enhancer. Transparent smooth and flexible films were characterized for weight, thickness uniformity, and drug content. Drug interactions with the polymer films were studied by differential scanning calorimetry, whereas X-ray diffraction was used to understand the drug polymorphism in the films. The in vitro drug release experiments were performed in phosphate buffer using the Keshary-Chien diffusion cell. Variations of drug release profiles were analyzed using the Ritger and Peppas empirical equation to describe the type of release mechanism. The exponent n values of the equation varied over the wide range of 0.75-2.23, suggesting non-Fickian to super Case-II type of diffusion transport. Statistical analyses of release data performed by the analysis of variance (ANOVA) method indicated significant differences within experimental measurements. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 1268-1274, 2011