Solid State Solubility of Miconazole in Poly[(ethylene glycol)-g-vinyl alcohol] Using Hot-Melt Extrusion

Abstract

The use of hot-melt extrusion for preparing homogeneous API-excipient mixtures is studied for miconazole-PEG-g-PVA [poly(ethylene glycol) - poly(vinyl alcohol) graft copolymer] solid dispersions with a 5 cm(3) table-top, twin-screw corotating microcompounder (DSM Xplore). Phase behavior of PEG-g-PVA, miscibility of miconazole in PEG-g-PVA and the partitioning of miconazole between PEG and PVA amorphous phases are characterized using a combination of modulated DSC, XRPD, and solid-state H-1 and C-13 NMR methods. The H-1 NMR transverse magnetization relaxation (T-2 relaxation) method is used to analyze the phase composition and molecular mobility of the copolymer. The T-2 relaxation decay of pure PEG-g-PVA can be described by four T-2 relaxation components in the temperature range studied. PVA crystallinity is not largely affected by hot-melt extrusion and the presence of the drug. Miconazole preferably resides in the PEG amorphous phase, and its molecules are well dispersed in the PEG-g-PVA matrix using hot-melt extrusion mixing. Miconazole forms amorphous nanoclusters whose average size equals approximately 1.6 nm, indicating solid solution formation (molecular level dispersion) of the drug in the polymer.