Implementing Quality by Design for Development and Optimization of Sublingual Tablet of Valsartan

Abstract

Purpose

Heart failure, a progressive cardiovascular disorder, significantly affects patient morbidity and mortality. Valsartan, an angiotensin II receptor antagonist, is widely used to mitigate the effects of heart failure, but its oral administration faces challenges such as poor solubility and variable bioavailability. The purpose of this study was to develop and enhance a sublingual fast-dissolving Valsartan tablet via excluding the gastrointestinal tract (GIT) and using a quality by design (QbD) approach to achieve fast drug dissolution.

Methods

A three-factor, two-level Box-Behnken Design (BBD) was employed to investigate the influence of Sodium Starch Glycolate (SSG), Crospovidone (CP), and Croscarmellose Sodium (CCS) on disintegration time (DT) and cumulative drug release. Response Surface Methodology (RSM) was used to model the interactions between these factors and optimize the formulation.

Results

The optimized formulation (OVSF-18) comprised 9 mg of SSG, 9 mg of CP, and 6.44 mg of CCS, achieving a rapid disintegration time of 33.33 seconds and a cumulative drug release of 92.33%. Statistical analysis confirmed the robustness of the model, with an Adjusted R² of 0.9961 for DT and 0.9806 for drug release, and a desirability score of 0.998. The formulation was validated experimentally, with minimal deviation from predicted values. This optimized sublingual tablet formulation addresses the limitations of oral administration by enhancing Valsartan’s bioavailability and therapeutic efficiency.

Conclusion

Unlike prior studies, this work presents a novel application of the QbD approach in developing sublingual tablets of Valsartan, achieving rapid disintegration and enhanced drug release. This optimized formulation is designed to address the urgent need for patient-centric dosage forms in heart failure management, providing a faster onset of action compared to conventional formulations.

This study introduces a novel application of the Quality by Design (QbD) approach to systematically develop and optimize sublingual tablets of Valsartan, addressing the limitations of conventional trial-and-error formulation methods. By employing Box-Behnken Design (BBD), the study achieved significant advancements in formulation performance, including rapid disintegration (within 33 seconds) and 92.33% drug release in 15 minutes. These results highlight the clinical relevance of the optimized formulation for providing rapid therapeutic action in heart failure management. This work bridges a critical gap in patient-centric sublingual dosage forms, offering a robust and reproducible approach for future pharmaceutical innovation.

Graphical abstract