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

Sandra Guns, Aswin Dereymaker, Pieterjan Kayaert, Vincent Mathot, Johan A Martens, Guy Van den Mooter

Index: Pharm. Res. 28 , 673-682, (2011)

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Abstract

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.The solid dispersions were prepared at different drug-polymer ratios and analyzed with modulated differential scanning calorimetry and X-ray powder diffraction.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.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.