Box-Behnken Optimized Olmesartan Sublingual Tablets: A Quality by Design Study

Background: Heart failure is a progressive cardiovascular condition associated with high morbidity and mortality. Although Olmesartan, an angiotensin II receptor antagonist, is effective in managing heart failure, its conventional oral route is limited by poor solubility and variable bioavailability.

Purpose: This study aimed to develop a fast-dissolving sublingual tablet of Olmesartan using a Quality by Design (QbD) framework, integrating Box–Behnken Design (BBD) optimization with ex vivo permeation analysis to enhance systemic absorption.

Methods: Three critical formulation variables—Sodium Starch Glycolate (SSG), Crospovidone (CP), and Croscarmellose Sodium (CCS)—were evaluated for their effect on disintegration time (DT) and cumulative drug release (CDR).

Result: The optimized formulation (OOSF-18), containing 9 mg SSG, 9 mg CP, and 6.44 mg CCS, exhibited a DT of 33.33 s and 92.33% CDR, with strong model predictability (adjusted R² = 0.9961 for DT and 0.9806 for CDR). Ex vivo permeation through porcine mucosa reached 89.76% within 10 min, indicating rapid transmucosal delivery potential. Stability studies confirmed formulation robustness over six months.

Conclusion: This combined QbD permeation strategy demonstrates a novel and efficient approach for improving Olmesartan’s bioavailability and offers translational potential for rapid-acting sublingual antihypertensive therapy.