Abstract

Supercritical carbon dioxide (SC-CO2), which combines the high diffusivity of a gas with the strong solvating power of a liquid, features mild critical conditions, high dissolution capacity, non-toxicity, and negligible solvent residues. These properties make it an important technological platform for micro/nanoscale drug particles formulation and pharmaceutical optimization. In this review, we provide a systematic overview of the mechanisms by which SC-CO2 functions as a solvent, antisolvent, and dispersion-assisting medium in micro/nanoscale drug particles formulation and drug optimization, and summarize the key factors and process characteristics governing micro/nanoscale drug particles formation. We highlight the advantages and recent advances of SC-CO2 in constructing carrier-based particles, producing carrier-free pure-drug particles, and improving drug dispersibility. By integrating representative applications such as surgical navigation and cancer therapy, we discuss SC-CO2's unique value in enhancing the bioavailability of poorly soluble drugs and facilitating clinical translation. Finally, we summarize the major challenges to industrialization and outline potential future strategies, aiming to provide theoretical guidance and technical insights for advancing SC-CO2 toward scalable pharmaceutical manufacturing.

文章链接：https://doi.org/10.1016/j.cclet.2026.11321