Abstract :
Aim and Objective: The main objective of the present research investigation is to formulate the sustained release
(SR) formulation of rosuvastatin. Rosuvastatin, an antihyperlipidemic agent, belongs to Biopharmaceutical
Classification System class-II agent. Materials and Methods: The SR tablets of rosuvastatin were prepared by
employing different concentrations of hydroxy methyl propyl cellulose (HPMCK4M) and sodium carboxymethyl
cellulose (SCMC) in different combinations by direct compression using 32 factorial designs. The concentration
of polymers, HPMCK4M, and SCMC required to achieve the desired drug release was selected as independent
variables, X1 and X2, respectively, whereas time required for 10% of drug dissolution (t10%), 50% (t50%), 75%
(t75%), and 90% (t90%) was selected as dependent variables. Results and Discussion: A total of nine formulations
were designed and are evaluated for hardness, friability, thickness, % drug content, and in vitro drug release. From
the results, it was concluded that all the formulations were found to be within the pharmacopeial limits and the
in vitro dissolution profiles of all formulations were fitted into different kinetic models; the statistical parameters
such as intercept, slope, and regression coefficient were calculated. Polynomial equations were developed for
dependent variables. The validity of developed polynomial equations was verified by designing 2 check point
formulations (C1 and C2). According to SUPAC guidelines, the formulation (F4) containing 30 mg of HPMCK4M
and 40 mg of SCMC is the most similar formulation (similarity factor f2= 89.561, dissimilarity factor f1 = 1.543,
and no significant difference, t = 0.0056) to marketed product (CRESTOR). Conclusion: The selected formulation
(F4) follows zero-order and Higuchi kinetics, and the mechanism of drug release was found to be non-Fickian
Diffusion (n = 0.963).
Keyword :
32 factorial design, Hydroxy methyl propyl cellulose K4M, non-Fickian diffusion mechanism, rosuvastatin, sodium carboxymethyl cellulose, SUPAC, sustained release tablet, zero-order kinetics