Design, Optimization, and Characterization of Orodispersible Doxofylline Tablets for Enhanced Pulmonary Drug Therapy

Doxofylline is a second-generation methylxanthine bronchodilator widely employed in the management of asthma and chronic obstructive pulmonary disease (COPD). Compared with theophylline, it demonstrates improved safety, reduced central nervous system stimulation, and minimal need for therapeutic drug monitoring. Despite its clinical advantages, conventional oral tablet formulations may present limitations in geriatric and dysphagic populations, particularly in acute respiratory distress scenarios where rapid onset and ease of administration are essential. Fast-dissolving tablets (FDTs), also referred to as orodispersible tablets, disintegrate rapidly in the oral cavity without the need for water and represent a patient-centric drug delivery platform. The present manuscript proposes a comprehensive development framework for 400 mg doxofylline fast-dissolving tablets using direct compression under a Quality by Design (QbD) paradigm. The formulation strategy integrates excipient compatibility assessment, preformulation characterization, superdisintegrant optimization using Box–Behnken experimental design, and dual analytical method validation employing both UV spectrophotometry and RP-HPLC as per ICH guidelines. Regulatory considerations, stability assessment protocols, and risk-based control strategies are also discussed. This review-cum-development framework provides a structured and regulatory-aligned approach for the formulation of doxofylline FDTs suitable for future experimental implementation and scale-up.