Engineering long-term antibacterial PLA packaging: Controlled release of thymol co-amorphous pairs via supercritical solvent impregnation

The rapid release of active compounds often limits the development of active food packaging with long-term antimicrobial effects. This study proposes an innovative and sustainable solution by integrating cocrystallization and supercritical fluid technologies to create a controlled-release system. Herein is investigated the impregnation of poly(lactic acid) (PLA) foams with thymol (THY) - phenazine (PHE) cocrystal pairs via supercritical solvent impregnation at 40 °C and 12–18 MPa, analyzing the impact of different isobaric cooling rates (0.3 and 1.5 °C/min) on particle deposition and release kinetics. Submicron THY-PHE co-amorphous pairs were successfully deposited within the PLA matrix, with particle size dependent on the cooling rate. These pairs exhibited significantly slower release kinetics than pure THY, with a release rate constant up to 12 times lower. Consequently, PLA foams loaded with THY-PHE pairs demonstrated prolonged antibacterial activity, completely inhibiting Staphylococcus aureus and Escherichia coli for up to 192 h with concentrations three times lower than those required for pure THY. This work presents a robust, environmentally friendly, method for engineering advanced packaging materials with tailored, long-term release of active agents. • Thymol-phenazine co-amorphous particles were deposited in PLA foams. • SSI with isobaric cooling allowed tailoring co-amorphous particle size in PLA foams. • The co-amorphous release constant was up to 17-fold lower than for thymol. • Active PLA completely inhibited the growth of S. aureus and E. coli up to 192 h. • Co-amorphous concentrations 12 times lower than thymol inhibited bacterial growth.