SYSTEMATIC FORMULATION DEVELOPMENT OF IMMEDIATE RELEASE TABLET DOSAGE FORM USING QUALITY BY DESIGN APPROACH

The main goal of this study was to develop a stable formulation of model antibacterial drug as an immediate-release tablet systematically using Quality by Design approach of which design of experiments is an integral part. The model drug was found to be a BCS class II drug official in USP having a plasma half-life of three to four hours. The formulation development work was initiated with wet granulation method and a total of three trials were conducted to determine the critical material attributes of the formulation used as factors for the experimental designs. The binder (Povidone K29/32,), Superdisintegrant (Crosscarmellose Sodium), Lubricant (Stearic acid and magnesium stearate), Pregelatinized Starch 1500 (binder and disintegrant) were determined to be critical for the formulation of the model antibacterial drug. A fractional factorial design (FFD) for four factors at two levels was selected to screen the varied response variable. A total of eight trials were conducted (24-1FFD). The four factors viz. Povidone K29/32 (X1), Crosscarmellose Sodium (X2), lubricant ratio (X3) and Pregelatinised starch 1500 IG: EG (X4) were varied as required by the experimental design and the factor levels were coded. (+1 for high and -1 for low). Disintegration time was taken as response variable. A central composite design (CCD) for two factors at three levels was selected to optimize the varied response variable. A total of thirteen trials were conducted. The two factors viz. PovidoneK29/32 (X1), Crosscarmellose Sodium (X2), were varied as required by the experimental design and the factor levels were coded. (+1 for high, 0 for moderate and -1 for low). Friability (5) and in vitro % drug release in 5 minutes (Q5) were taken as response variables. The formulated tablets were evaluated for various precompression parameters like bulk density, tapped density, Carr's index, Hausner's ratio and post compression parameters like thickness, hardness, weight variation, friability, disintegration test and in vitro drug release studies. From this study, it was concluded that optimized formulation containing Crosscarmellose Sodium (8.16%) and Povidone K29/32 (1.37%) showed satisfactory friability, in vitro % drug release at 5 mins (Q5) and other physical characteristics of immediate release tablets. A design space was created using desired levels of response variables. A composition was selected within design space as optimized formulation and internally validated. Linear correlation plots were drawn for the predicted and observed responses.