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.

Objectives: The objective of the research was to develop and evaluate the multiparticulate pulsatile release minitablets of verapamil hydrochloride for the treatment of hypertension at a desired time to mimic the circadian rhythms and improve the patient compliance. Materials and Methods: Formulation was prepared by CODAS technology. It was designed to initiate the release of verapamil after 4h lag time and reached the therapeutic levels at in the early morning hours, when the blood pressure is at its highest. The core minitablets were prepared by wet granulation process and coated with water insoluble polymer like ethylcellulose along with hydrophilic plasticizer. The formulation attributes were optimized and evaluated the in vitro performance. Results: The in vitro dissolution studies revealed that the coating build-up of ethylcellulose controls the initial lag time and release rate of drug product. Among the formulations (F1a) 10% w/w ethylcellulose coated minitablets showed lag time for 4 hr and controlled the release up to 24 hr. The formulation optimization studies illumined the critical attributes like fumaric acid (F2), which modified the microenvironment and improved the dissolution profile of drug product in phosphate buffer. The optimized formulation (F1a) was compared against the marketed product (CALAPTIN 120 mg SR tablets) and observed that the dissolution behaviour of the drug product followed first-order kinetics. Conclusion:The outcomes were presumed that the pulsatile release has been accomplished from coated minitablets with a lag time of 4hr, which is reliable with the demands of the chronotherapeutic drug delivery by efficiently control the blood pressure at early morning.