| The formation of porous microspheres loaded with peptide using solvent extraction/evaporation methods involves intrinsic variables, such as solvent-polymer interaction parameters, and extrinsic variables, such as dispersed phase (DP)/continuous phase (CP) ratio, temperature and DP 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 DP was based on diffusion theory and a function of the driving force of chemical potential gradient and transport parameters. The solvent removal process involved solvent diffusion in the DP followed by evaporation at the CP/air interface. The process can be facilitated by forced convective flow. Mathematically, the process can be expressed by coupling the equations for mass transfer in the DP and first order evaporation from the CP. Two phase transitions, the viscous and glassy boundaries were used to represent the phase transitions in the polymer solution (DP).; Based on the mathematical model and experimental results, rapid solvent removal resulted in large pore size, lower surface area, thicker periphery and higher residual solvent; the rate and extent of hardening of the periphery of the microspheres played a major role in the ultimate internal structure. Slow solvent removal gave rise to the opposite properties of microsphere; the homogenous distribution of the DP composition and delay of hardening are believed to be the major causes. The extrinsic variables, which are manageable, can be varied to obtain the desired rate of solvent removal during microsphere formation and the mathematical model can be used to simulate such conditions. Low D/C ratio, high CP-replacement rate, high temperature, high heating rate and high polymer concentration contribute to enhanced solvent removal. |
