Quality by design based development and optimization of novel gastroretentive floating osmotic capsules of clopidogrel bisulfate

The aim of the present investigation was to develop and optimize gastroretentive floating osmotic formulation of clopidogrel bisulfate using risk based approach. Risk assessment was carried out using failure mode effect analysis (FMEA) and high risk factors were identified. Preliminary studies highlighted importance of selection of low molecular weight PEO (molecular weight ~ 100,000) as rate controlling polymer and band sealing of coated capsules whereas thermal characterization studies assisted in selection of hydrogenated castor oil as more compatible lubricant. A face centered central composite design (CCD) was deployed to optimize high risk factors i.e. amount of osmogen (sodium chloride), amount of rate controlling polymer (Polyethylene oxide), polymer (Cellulose acetate) to plasticizer (PEG 3350) ratio in semipermeable membrane and weight gain per unit surface area. Optimized formulation was selected using constraint based graphical optimization technique and desirability function. Optimized batch was also found to be stable under selected packaging configurations. Optimized batch exhibited dissolution at 1 h of 4.65%, 4 h of 31.23%, 8 h of 62.80%, 12 h of 94.55% with zero floating lag time and total buoyancy time of more than 12 h. Scanning electron microscopy (SEM) was carried out to characterize semipermeable coating membrane before and after dissolution studies. Capability indices of six reproducible batches illustrated capability of selected process for manufacturing batches as per desired specifications. Overall, present investigation successfully illustrated development and optimization of novel hard gelatin capsule based gastroretentive floating osmotic formulation of clopidogrel bisulfate with zero order drug release profile and improved patient compliance. © 2018, The Korean Society of Pharmaceutical Sciences and Technology.