Formulation and Optimization of Trandolapril Oro-dispersible Tablets Using the Quality by Design (QbD) Approach

Abstract

Introduction: This study aims to use a Quality by Design (QbD) approach to formulate and optimize Trandolapriloro-dispersible tablets. The central composite design tool was utilized to assess the scientific understanding of independent input variables and output responses to construct a design space for regulatory flexibility. Oro-dispersible Tablets (ODT) can also be used to deliver drugs directly to the oral mucosa, bypassing first-pass hepatic metabolism and potentially accelerating the process. Methodology: The concentrations of super disintegrant and dry compressible binder were selected as independent variables. Disintegration time in seconds and % friability was selected as dependent variables. Polynomial equations were used to predict the quantitative effect of independent variables at various levels on response variables. Results and Discussion: The pre-compression parameters suggested that the flow characteristics were quite excellent. All tablets prepared in the above experiments were evaluated for pharmaco-technical properties and found to be within the required limits using the direct compression method. The angle of repose of the dry blends from each formulation batch (F1 to F9) ranged from 29.03° to 33.67°. All formulation batches had a loose bulk density of 0.31 + 0.07 to 0.37 + 0.91 g/cm3 and a tapped density of 0.41+ 0.02 to 0.46+ 0.16 g/cm3, respectively. The compressibility index was determined to be between 1.65 + 0.17 to 19.93 + 0.47 . Hausner's ratio was between 1.14 + 0.88 to 1.19 + 0.32. The thickness of the tablets ranged from 2.07 + 0.54 to 2.52 + 0.12 mm. The tablets were found to have a hardness of 3.08 + 0.14 to 3.67 + 0.41 kg/cm2. The weight of the tablets prepared ranged from 50 + 0.09 to 52 + 0.56 mg on average. Tablet friability was 0.52 + 0.54 to 0.83 + 0.10 %, and the disintegration time ranged between 27 and 58 seconds. All of these parameters were found under the acceptable limit of pharmacopoeias. The increase of Crospovidone concentration decreased the disintegration time and increased % friability. Whereas increasing the concentration of microcrystalline cellulose increased the disintegration time and decreased the % friability. Contour plots clarified the link between independent and dependent variables. The most cost-effective batch was chosen based on these plots within the desired range because the actual and projected values suggested by the full model were very close to each other; the statistical model is mathematically valid. Conclusion: The results showed that the proposed design for developing trandolapriloro-dispersible tablets with optimal properties was effective.