Author & Research Contributor
Published in 2026 | VOLUME 03, AUGUST ISSUE 08Poor aqueous solubility among clinically essential antibiotics represents a formulation challenge with consequences that extend beyond compromised bioavailability into the pharmacodynamic domain of antimicrobial resistance, where dissolution-imposed sub-therapeutic drug exposure generates selective pressure for resistance emergence. Despite decades of regulatory success applying amorphous solid dispersion technology to antiviral and antineoplastic drug classes, its systematic application to poorly soluble antibiotics remains disproportionately underdeveloped. This review examines the physicochemical principles underlying amorphous solid dispersion performance, including the thermodynamic basis of supersaturation generation, glass transition-mediated solid-state stabilization, and the spring-and-parachute mechanism of gastrointestinal drug release. A science-based polymer selection framework is presented, comparing the properties, drug interaction mechanisms, and processing suitability of vinyl-based, cellulosic, and polymethacrylate carrier families across the physicochemical landscape of antibiotic molecules. Manufacturing considerations specific to thermolabile and high-melting-point antibiotics are addressed, with analysis of hot melt extrusion, spray drying, and KinetiSol approaches and their respective constraints. Translational evidence from itraconazole, griseofulvin, rifampicin, and posaconazole amorphous solid dispersion systems is critically evaluated, including dissolution enhancement, pharmacokinetic outcomes, and in vitro–in vivo correlation data. Physical stability requirements, ICH-compliant storage protocols, and the regulatory landscape for approved formulations are examined. Emerging directions encompassing machine learning-assisted polymer screening and ternary dispersion architectures are identified as strategic priorities. Applying this formulation framework systematically to poorly soluble antibiotics represents a scientifically compelling and clinically urgent contribution to antimicrobial therapy.
amorphous solid dispersion: antimicrobial agents: biopharmaceutics classification system: drug-polymer miscibility: oral bioavailability: supersaturation.