Abstract

This study investigates the feasibility of directly compressing high doses of metformin hydrochloride despite its poor compressibility. With regards to clearly outlined scientific principles, Quality by Design places a great emphasis on the systematic development of products. However, it is highly helpful and essential to understanding the causes and the interactions between the product components through a set of desired tests. Metformin hydrochloride powder was compressed using flat faced Euro B punch of 15 mm diameter, using Compaction Simulator (Stylcam 200R) at different compaction forces. Quality control tests were done on the compressed tablets and were evaluated. Utilizing the quality by design method with Umetric MODDE software, the necessity to develop direct compressible metformin hydrochloride was addressed. Tablet tensile strength, friability and disintegration time were evaluated. The effect of formulation components and variables was assessed. Binder types implemented as a singular unit or as combination showed their effect on formulation. By evaluating the variations in formulations and optimization of metformin hydrochloride, a design space was established through the identification of the critical process parameters, critical quality attributes, and the risk assessment with the aid of Modde Pro 12.1 software. Design of experiment was applied for a better understanding of the interactions between formulation variables and process parameters to achieve an optimum formulation. Metformin hydrochloride was successfully developed by direct compression and the simultaneous application of quality by design assisted in obtaining a robust formulation.