FORMULATION DEVELOPMENT AND STATISTICAL OPTIMIZATION OF IVABRADINE HYDROCHLORIDE FLOATING PULSATILE PELLETS BY FLUIDIZED BED COATING TECHNIQUE

ABSTRACTObjective: The objective of the current work was to develop Ivabradine hydrochloride (HCl) floating pulsatile pellets containing drug loaded calciumalginate pellets coated with pH-dependent polymer Eudragit S100 oil dispersion.Methods: Fluidized bed coating technique was used to develop pellets. A 2factorial design was employed to study the effect of independent variables(inlet air temperature, spray rate), on dependent variables (% entrapment efficiency, % friability, and average particle size). Optimization was doneby fitting experimental data to the software program (Minitab). Obtained pellets were subjected to different evaluation parameters which are criticalin the development of the dosage form. An in vitro lag phase study was carried out for all batches in simulated gastric fluid (0.1N HCl) for 5 hrs andin vitro drug release study was carried out for optimized batch (B4) of two different sizes (10/12#, 12/16#) in simulated intestinal fluid (pH 7.4phosphate buffer).2 Results: The optimized batch (B4) showed satisfactory % entrapment efficiency of 92.66±1.52; % friability of 0.57±0.03; and average particle sizeof 1424±16 (µm). All batches maintained lag phase for 5 hrs in 0.1N HCl. An optimized batch of two different sizes exhibited a burst release within30 minutes in simulated intestinal fluid with no significant difference in release rate constant (*p>0.05) and followed first order kinetics.Conclusion: Thus, ivabradine HCl floating pulsatile pellets was successfully developed for treating angina pectoris which is an underlying cause ofheart attack by fluidized bed coating technique employing factorial design.Keywords: Ivabradine hydrochloride, Sodium alginate, Eudragit S100, Pellets, Fluidized bed coating, Optimization, Central composite desig