International Journal of Pharmaceutical Research and Innovation, Vol. 2: 1-8, 2011
Stable and bioequivalent formulation development of highly acid labile proton pump inhibitor: Rabeprazole
A. Mukharya, S.A. Chaudhary, A. Bheda, A. Mulay, N.Mansuri, N. Laddha, A. K. Misra
Formulation Development Department, Cadila Pharmaceuticals Limited, 1389, Trasad Road, Dholka, Ahmedabad, Pin Code: 387 810. India.
Abstract Rabeprazole sodium is a Proton-Pump-Inhibitor (PPI), used for treatment of acidity by inhibiting H+/K+/ATPase pump at the gastric parietal secretary cells. The main challenge in the formulation of Rabeprazole is to prevent degradation of Active Pharmaceutical Ingredient (API) upon exposure to acidic environment or moisture. In order to prevent acid degradation of API in Gastro Intestinal Tract (GIT), tablets should be enteric coated to prevent its exposure to gastric acid. Coating of acid labile PPI with enteric coating acidic material may further cause the decomposition of acid labile PPI. In order to overcome this limitation, the core containing acid labile PPI and alkalizers was seal coated with water-insoluble polymer and non-hygroscopic alkalizer (stabilizer) and subsequently enteric coating was done on seal coated tablet, with a polymer to prevent its exposure to acidic environment of GIT and facilitate absorption through intestinal fluid. The optimized formulation was packed in Alu-Alu blister and charged for stability study at 40°C/75%RH. It was observed that over 6 months the formulation was stable with impurities in control. In vivo bio-equivalence study was performed, in which optimized formulation was found bio-equivalent with marketed reference formulation.
Keywords: Bio-equivalence, Enteric-coating, Rabeprazole, Seal-coating, Stability.