Quality by design: understanding the formulation variables and optimization of metformin hydrochloride 750 mg sustained release tablet by Box–Behnken design

This study examined the formulation variables and optimization of a sustained-release metformin hydrochloride 750 mg tablet using a combination of hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP K30), and glyceryl behenate with a computer optimization technique based on a response surface methodology (RSM) utilizing a polynomial equation. A three-factor, three-level Box–Behnken design was used for the optimization procedure with the contents of HPMC ( X 1 ), PVP K30 ( X 2 ), and glyceryl behenate ( X 3 ) as independent variables. The drug release percentages at 1, 3, and 10 h were the target responses and were restricted to 25–35 % ( Y 1 ), 55–65 % ( Y 2 ), and 85–100 % ( Y 3 ), respectively. The quadratic model fit the data well and the resulting equation was used to predict the responses in the optimal region. The optimized formulation was achieved with 165 mg HPMC, 40 mg PVP K30, and 22.5 mg glyceryl behenate, and the observed responses of the optimized formulation were very close to the values predicted using the RSM optimization technique. Furthermore, the drug release rate and dissolution curve shape of the optimized formulation were similar to those of the commercial product.