Development and optimization of intermediate release ketoprofen tablets by central composite design

Abstract

In this study cost effective direct compression technique was used for the development and optimization of intermediate release (IntR) ketoprofen tablets using central composite design (CCRD). Fifteen different formulations (F1-F15) were developed using (X1) microcrystalline cellulose (Avicel PH-102) (18-51%), (X2) methocel K4M (0.1- 25%) and (X3) starch (1.5-18%) as selected variables while responses were % friability and Carr’s Index (compressibility index). Powder blends of all formulations were evaluated using Angle of Repose, Carr’s Index and porosity. Results of powder blends comply with USP standards and are classified as Fair Excellent. From F1-F15 only four formulations i.e. F6, F7, F14 and F15 were selected on acceptable weight basis, micromeritic properties and on the concentration of excipients. For the assessment of physico chemical properties of the optimized formulations different tests were performed. All results were found to be adequate range. In vitro assessment of the optimized formulations were also carried out in different dissolution media i.e. pH 1.2, phosphate buffer 4.5, pH 6.8 and pH 7.5. Release behaviour of F6, F7, F14 and F15 were estimated by using one - way ANOVA, model - independent, model dependent methods. Results of f1 and f2 showed that all the test formulations i.e. F6, F7, F14 were found to be similar with the reference formulation i.e. F15 at various dissolution media. Also all the formulations followed Hixson-Crowell kinetic model. The parameter n showed Anomalous transport (non - fickian diffusion). The mean dissolution time (MDT) was found to be in the range of 2.632-2.922. Results of ANOVA indicated no significant difference within and between formulations at different dissolution media as p values were found to be >0.05. Also all the selected formulations were found to be stable at accelerated conditions.