STATISTICAL DESIGN OF EXPERIMENT-BASED FORMULATION DEVELOPMENT AND OPTIMIZATION OF FLOATING MATRIX TABLET OF ANTI-EMETIC DRUG

Abstract

Objective: To employ Design of Experiment (DOE) for designing a floating matrix tablet of Domperidone Maleate (DM) using novel direct compression grade polymer METHOCEL K4M DC2 that offers advantages of extended or sustained release, providing for cost-effective manufacturing. Methods: To prepare floating matrix tablets containing DM, the direct compression method was employed. The tablets were optimised using a 22 Central Composite Design (CCD). Concentration of the sustained release polymer METHOCEL DC2 K4M grade (X1= A) and Concentration of the floating agent potassium bicarbonate (KHCO3) (X2= B) were the independent variables selected whereas floating lag time (Y1), drug release at 1 h (Y2), 4 h (Y3), 6 h (Y4) and 8 h (Y5) were the 5 dependent variables employed in the study design. Fourier Transform Infrared (FTIR) analysis was utilised to analyse drug-excipient compatibility, revealing no discernible interaction, and various mathematical models were employed to study the drug release mechanism. Results: The prepared tablets were evaluated for weight, thickness, hardness, friability, and assay and the results were found to be satisfactory. The optimised formulation predicted by the software was found to have a desirability value of 0.982, containing 60 mg of METHOCEL DC2 K4M and 20 mg of KHCO3, was prepared and evaluated. Predicted and experimental results were found to be comparable for all the responses. All formulations were shown to fit well into Zero-order release kinetics, but the optimised formulation (F4), with R2= 0.9893 and n= 2.2797, exhibited the best fitting in both the Zero-order and Korsmeyers-Peppas model. Conclusion: The study conducted revealed that floating tablets of DM could be developed using KHCO3 as a gas-generating agent with sustained drug release till 14 h using polymer METHOCEL DC2 K4M.