The objective of the present study is to develop, evaluate and optimize colon targeted tablets of ornidazole. For this aim, the core tablets containing ornidazole were compression coated with different polymer mixtures and subjected to quality control studies. Thereafter, swelling, erosion and dissolution studies were performed under conditions mimicking mouth to colon transit. The results of in vitro studies showed that all of the compression coated tablet formulations prevented the drug release in mimicking conditions of stomach and small intestine. On the other hand, only the tablets that were compression coated with pectin and ethyl cellulose (EC) mixtures provided high ratio of drug release (up to 96%) during 24 h in colonic medium. Thereafter, the release kinetics of all formulations were investigated according to zero order kinetic model and the highest r(2) value (0.967) was found to belong the formulation compression coated with 80% pectin and 20% EC N10 mixture. Finally, the large amount of in vitro experimental data obtained in this study was evaluated with artificial neural network (ANN) programme to optimize the best-fit formulation. The results obtained from ANN studies were similar with in vitro evaluation results but they were more accurate. According to ANN evaluation, tablets compression coated with 79.024% pectin and 20.976% EC N10 mixture was found to be the most likely formulation to provide targeting ornidazole for local action in the colon.