Development of a Dual-Targeted Oral Delivery System for Mesalazine and Acetaminophen

Inflammatory bowel diseases (IBD) are chronic and recurrent inflammatory disorders of the gastrointestinal tract, classified into two main categories: ulcerative colitis and Crohn's disease. Mesalazine is the most commonly prescribed drug for the treatment of inflammatory bowel disease (IBD); however, its rapid absorption in the small intestine reduces its local effects in the colon. The use of mesalazine in coated pellet form as a multi-unit drug delivery system may enhance its effectiveness compared to conventional pharmaceutical forms such as tablets. Arthritis is one of the extra-intestinal manifestations of IBD, which can be alleviated by acetaminophen. The aim of this study is to design a multi-unit oral drug delivery system (pellets) that simultaneously delivers mesalazine to the large intestine and acetaminophen to the stomach.

In this experimental study, mesalazine pellets were prepared using the extrusion-spheronization method and coated with pH-dependent polymers (Eudragit® L100 and Eudragit® S100) as well as a combination of time-dependent (Eudragit® RS) and pH-dependent polymers (Eudragit® L100). Drug release was evaluated in simulated gastrointestinal environments, and the optimal formulations were identified. Subsequently, acetaminophen was loaded onto the optimized pellets using a fluid bed coater. The drug release profile was assessed using a continuous dissolution testing method. Thermal analysis, infrared spectroscopy, mechanical testing and scanning electron microscopy were performed to evaluate the physicochemical properties and investigate potential interactions.

Pellets coated with 40% Eudragit® RS and 60% Eudragit® L100, as well as those coated with 100% Eudragit® S100, were found to be more suitable for colon drug delivery than other formulations. Continuous dissolution testing showed that acetaminophen was released in a pH 1.2 environment within 2 hours, while mesalazine remained intact and reached the large intestine. Physicochemical tests indicated that the pellets had a smooth surface, uniform coating, and appropriate hardness, with no detectable interactions between the drugs and excipients.

This study demonstrated that the optimized formulation effectively enables the targeted delivery of acetaminophen to the stomach and mesalazine to the colon in a single dosage form.