Formulation and Evaluation of pH-Responsive Mini-Tablets for Ileo-Colonic Targeted Drug Delivery

Purpose: To formulate and evaluate a novel pH-responsive mini-tablet for ileo-colonic targeted delivery of naproxen in chronotherapeutic treatment of rheumatoid arthritis.Methods: Core mini-tablets were prepared by direct compression method. These prepared core minitablets were then coated with enteric coating polymers, i.e., Eudragit L100 and Eudragit S100 in different ratios and concentrations and filled into an empty hydroxypropyl methylcellulose (HPMC) capsule. Fourier transform infrared spectroscopy (FTIR) and diffraction scanning calorimetry (DSC) studies on the pure drug and its combination with polymers were performed to assess compatibility. The formulations were also characterized for drug content, in-vitro drug release and stability.Results: FTIR and DSC data show that there was no interaction between the drug and the polymers. All the physicochemical properties of the core mini-tablets were within acceptable limits. Drug content was 99.42 ± 0.15 %. Optimized formulation F12 released drug after a lag time of 5.02 ± 0.4 h, with 99.40 ± 0.4 % of the drug released at the end of 8 h. It was also stable for a period of 6 months based on International Conference on Harmonization ICH guidelines.Conclusion: A novel pH-responsive mini-tablet formulation of naproxen has been successfully developed for the chronotherapeutic treatment of rheumatoid arthritisKeywords: Ileo-colonic targeted delivery, Naproxen, Mini-tablets, Hydroxypropyl methylcellulose , Chronotherapeutic, Enteric coat, Rheumatoid arthriti