Formulation and evaluation of ileo-colonic targeted matrix-mini-tablets of Naproxen for chronotherapeutic treatment of rheumatoid arthritis

Abstract

In this present research work, the aim was to develop ileo-colonic targeted matrix-mini-tablets-filled capsule system of Naproxen for chronotherapeutic treatment of Rheumatoid Arthritis. So Matrix-mini-tablets of Naproxen were prepared using microsomal enzyme dependent and pH-sensitive polymers by direct compression method which were further filled into an empty HPMC capsule. The compatibility was assessed using FT-IR and DSC studies for pure drug, polymers and their physical mixtures. The prepared batches were subjected to physicochemical studies, drug content estimation, in-vitro drug release and stability studies. When FTIR and DSC studies were performed, it was found that there was no interaction between Naproxen and polymers used. The physicochemical properties of all the prepared matrix-mini-tablets batches were found to be in limits. The drug content percentage in the optimized formulation F18 was found to be 99.24 ± 0.10%. Our optimized matrix-mini-tablets-filled-capsule formulation F18 releases Naproxen after a lag time of 2.45 ± 0.97 h and 27.30 ± 0.86%, 92.59 ± 0.47%, 99.38 ± 0.69% at the end of 5, 8, 12 h respectively. This formulation was also found to be stable as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. Thus, a novel ileo-colonic targeted delivery system of Naproxen was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis. Keywords: Matrix-mini-tablets, Naproxen, Microsomal enzyme dependent polymers, pH-sensitive polymers, Chronotherapy, HPMC capsule