Formulation and Optimization of In-Situ Buffered Formulation Containing Indomethacin In Combination With Pantoprazole

ABSTRACTIn-Situ buffer formulation contain agents which immediately buffer the internal environment of the body and increases the stability of acid labile drugs inside the body. Here this approach is used for making combination capsule formulation to reduce the side effects of Nonsteroidal anti-inflammatory drugs. Pantoprazole is an acid labile drug which is very useful for the prevention and treatment of NSAID related gastric ulcer, so to reduce its side effects this approach was used. In this Indomethacin is used as Nonsteroidal anti-inflammatory drugs. For this purpose, macroenvironment buffering method was used. Based on their acid neutralizing capacity the best buffering combination was selected. In this method immediate release excipients or superdisintegarnts (SSG & CCS) whereas rate retarding polymers (Guar gum, Xanthan gum & ethyl cellulose) were added in the formula.  Ex vivo permeation study was performed by using Non-everted intestinal sac method in selected optimized batch. For optimization full factorial 23 design was used along with mathematical models. Prepared optimized formulation was compared with marketed formulation. Final pH from optimized formulation was found to be 5 to 6. The prepared optimized capsule is having 98.86% immediate release of pantoprazole sodium sesquihydrate upto 30 min and 99.84% sustain release of indomethacin upto 12 hrs. The prepared formulation showed immediate release of stable pantoprazole sodium sesquihydrate (due to the presence of in-situ buffering agents inside the capsule) along with the sustained release Indomethacin with very less adverse effects. Keywords: Stable pantoprazole sodium sesquihydrate, sustained release, macroenvironment, Ex vivo permeation.