Statistical optimization of alginate-based oral dosage form of 5-aminosalicylic acid aimed to colonic delivery: In vitro and in vivo evaluation

Abstract

Although different colon-targeting methods such as pH and time-dependent as well as bacterially degradable systems have been developed, due to variations in physiological conditions of patients, one system alone cannot produce a reliable drug delivery system. Therefore, in this study, an attempt was made to formulate 5-ASA pellets based on a combination of pH and time-dependent systems. A 32 full-factorial design was used to evaluate the effect of sodium alginate (SA) concentration and the polymer ratio (Eudragit® RS: Eudragit® S100) on morphology, mechanical features and release behaviour of 5-ASA pellet formulations. Fourier transform infrared spectroscopy, and differential scanning calorimetry analysis ruled out any interactions between the formulations components. The optimized formulation released 35, 55 and 89% of the drug within 15 h, at pHs 1.2, 6.8 and 7.4, respectively. In vivo studies demonstrated that the administration of sodium alginate-based matrix pellets containing 5-ASA coated with ES100 was effective in alleviating the damaged tissues and also decreased the inflammatory score and the rate of weight loss in colitis rats. The results indicated the remarkable anti-inflammatory efficacy of the designed colonic delivery system and the proposed formulations can be further developed in the pharmaceutical industry for patient use.