Comparison between hot-melt extrusion and spray-drying for manufacturing solid dispersions of the graft copolymer of ethylene glycol and vinylalcohol.

PURPOSE: To investigate the effect of the manufacturing method (spray-drying or hot-melt extrusion) on the kinetic miscibility of miconazole and the graft copolymer poly(ethyleneglycol-g-vinylalcohol). The effect of heat pre-treatment of solutions used for spray-drying and the use of spray-dried copolymer as excipient for hot-melt extrusion was investigated.
METHOD: The solid dispersions were prepared at different drug-polymer ratios and analyzed with modulated differential scanning calorimetry and X-ray powder diffraction.
RESULTS: Miconazole either mixed with the PEG-fraction of the copolymer or crystallized in the same or a different polymorph as the starting material. The kinetic miscibility was higher for the solid dispersions obtained from solutions which were pre-heated compared to those spray-dried from solutions at ambient temperature. Hot-melt extrusion resulted in an even higher mixing capability. Here the use of the spray-dried copolymer did not show any benefit concerning the kinetic miscibility of the drug and copolymer, but it resulted in a remarkable decrease in the torque experienced by the extruder allowing extrusion at lower temperature and torque.
CONCLUSION: The manufacturing method has an influence on the mixing capacity and phase behavior of solid dispersions. Heat pre-treatment of the solutions before spray-drying can result in a higher kinetic miscibility. Amorphization of the copolymer by spray-drying before using it as an excipient for hot-melt extrusion can be a manufacturing benefit.