Systematic formulation development of once-a-day gastroretentive controlled release tablets of rivastigmine using optimized polymer blends

Rivastigmine is a drug extensively prescribed for the treatment of Alzheimer’s disease. On therapeutic fronts, severe gastrointestinal (GI) adverse effects owing to a rapid rise and fall in drug plasma levels, and the high frequency of its dosing, tend to limit its usage. The present investigation, therefore, aimed at developing a gastroretentive floating-bioadhesive CR formulation for delivering rivastigmine in a sustained manner at the desired site of absorption. Employing 7-factor Taguchi design, the influential factors were embarked upon as Carbopol 971P and Methocel K15M CR. Effervescent floating-bioadhesive hydrophilic matrices were systematically formulated using a face-centered cube design (FCCD) and evaluated for in vitro drug release, floatation and ex vivo bioadhesive strength. Optimal composition of polymer blends systematically chosen using brute-force methodology, overlay plots and desirability function exhibited excellent bioadhesive and floatational characteristics besides possessing adequate drug release control (T60 > 5 h). Pharmacokinetic studies carried out in rabbits showed the absence of any sharp peaks or troughs in the plasma drug levels, and various levels of in vitro/in vivo correlation (IVIVC) were successfully established. In vivo gamma scintigraphic studies in human volunteers ratified the gastroretentive characteristics of the optimized formulation with retention time of 6 h or more. Thus, besides unraveling the polymer synergism, the study helped in developing an optimal once-a-day gastroretentive drug delivery system exhibiting excellent swelling, floating, and bioadhesive characteristics.