Kinetic and thermodynamic modeling of the formation of polymeric microspheres using solvent extraction/evaporation method

The formation of polylactide-co-glycolide microspheres loaded with a peptide using solvent extraction/evaporation methods involves intrinsic variables, such as solvent-polymer interaction parameters, and extrinsic variables, such as dispersed phase/continuous phase ratio, temperature and dispersed phase composition. A mathematical model based on mass transfer was developed by incorporating these variables, and, by superimposing with the state of phase transition, the model was used to predict the microsphere properties. The mass transfer in the dispersed phase was based on diffusion theory and was a function of the driving force of chemical potential gradient and transport parameters. The solvent removal process involved solvent diffusion out of the dispersed phase followed by evaporation at the continuous phase/air interface, a process which can be facilitated by forced convective flow. Mathematically, the process can be expressed by coupling the equations for mass transfer in the dispersed phase and first order evaporation from the continuous phase. Two phase transitions, the viscous and glassy boundaries, were used to represent the phase transitions in the polymer solution. The phase transition can be superimposed on the composition profile in the dispersed phase; the solidification of microsphere can be evaluated from such a treatment.