Hydrophilic polymers matrix systems of Nifedipine sustained release matrix tablets: Formulation optimization by Response Surface Method (Box-Behnken technique)

The modified release matrix dosage form is preferred in order to avoid fluctuations in the blood levels, which was observed in the drug Nifedipine. The aim of the present research was to formulate a sustained release matrix dosage form of Nifedipine, a potent therapeutic agent for cardiovascular disease, which primarily reduce the occurrence of steep rises in plasma concentration of drug, by using different polymers to achieve better bioavailability and also to reduce dosing frequency and side-effects employing response surface methodology by incorporating a 3-factor, 3-level Box-Behnken statistical design. Dependent variables are the release retardant polymers such as HPMC K15M (X1), HPMC E10 CR Prem. (X2), and Sodium Alginate (X3) and Independent variables are the percentage drug release at 1 h (Y1), percentage drug release at 8 h (Y2) and hardness (Y3) were studied. Box-Behnken response surface plots were drawn, statistical validity of the second order and quadratic models were established and the optimized formulations was chosen based on feasibility and grid search. The physical evaluation and in-vitro release studies were performed on all the formulations and the data were fitted to different release kinetic equations such as zero order, first order, Higuchi, Hixson Crowell and Korsemayer-peppas in terms of r2 and n-value. Validation of the optimization study with 13 confirmatory runs indicated high degree of prophetic ability of response surface methodology. From the confirmatory runs, the optimized formulation showed gradual sustained release (best fit model–peppas, n=0.44) by Fickian diffusion process. This design facilitated the optimization of Nifedipine sustained release matrix dosage form to achieve better bioavailability.

Author(s): Prabakaran L, and Vishalini M

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