Analytical Tools Used for Characterization and Development of Minitablets: A Verapamil Hydrochloride Case Study

Abstract

Various analytical techniques were used at different stages of formulation development to assess the interactions and quality throughout the lifecycle of the verapamil hydrochloride minitablets (VHMT). At initial stage of development studies, pre-formulation analytical techniques like Fourier transform infrared (FTIR) and Differential scanning calorimetry (DSC) used to evaluate the interactions between the drug substance with different inactive ingredients and physicochemical properties of drug substance, which provided the groundwork for the development of robust formulation. A part of physicochemical properties, the solubility data of verapamil hydrochloride (VH) exhibited that pH dependent solubility throughout the physiological buffer media from pH 1.2 – 6.8, as pH of media increase solubility decrease due to the weak basic nature of VH. To improve the solubility of VH, fumaric acid was included in the formulation. The analytical data of FTIR and DSC showed that no chemical interaction with selected excipients. The formulation analytical quantitative techniques like a stability indicating HPLC assay procedure has been developed and validated for VHMT life cycle (initial and stability samples). The analytical data of stability samples of VHMT showed stable upto 3M at 40°C. The pre-formulation data at initial development stage and the stability data of final product evidences that the final drug product was developed with desired release characteristics without any instability issues. In conclusion, the combined use of pre-formulation and formulation analytical techniques helped to identify the defects at early stage of development and overcome those shortcomings by appropriate scientific approach, which significantly minimized the formulation failure at later stage.