Solid Dosage Forms of Biopharmaceuticals in Drug Delivery Systems Using Sustainable Strategies

Drug delivery systems (DDS) often comprise biopharmaceuticals in aqueous form, making them susceptible to physical and chemical degradation, and therefore requiring low temperature storage in cold supply and distribution chains. Freeze-drying, spray-drying, and spray-freeze-drying are some of the techniques used to convert biopharmaceuticals-loaded DDS from aqueous to solid dosage forms. However, the risk exists that shear and heat stress during processing may provoke DDS damage and efficacy loss. Supercritical fluids (SCF), specifically, supercritical carbon dioxide (scCO₂), is a sustainable alternative to common techniques. Due to its moderately critical and tunable properties and thermodynamic behavior, scCO₂ has aroused scientific and industrial interest. Therefore, this article reviews scCO₂-based techniques used over the year in the production of solid biopharmaceutical dosage forms. Looking particularly at the use of scCO₂ in each of its potential roles-as a solvent, co-solvent, anti-solvent, or co-solute. It ends with a comparison between the compound's stability using supercritical CO₂-assisted atomization/spray-drying and conventional drying.