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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/14311

Title: Solid State Solubility of Miconazole in Poly[(ethylene glycol)-g-vinyl alcohol] Using Hot-Melt Extrusion
Authors: Litvinov, V. M.
Guns, S.
Scholtens, B. J. R.
Quaedflieg, M. P.
Van den Mooter, G.
Issue Date: 2012
Citation: MOLECULAR PHARMACEUTICS, 9 (10), p. 2924-2932
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.
Notes: [Guns, S.; Van den Mooter, G.] Katholieke Univ Leuven, Lab Pharmacotechnol & Biopharm, B-3000 Louvain, Belgium. [Litvinov, V. M.] DSM Resolve, NL-6160 MD Geleen, Netherlands. [Adriaensens, P.; Carleer, R.] Hasselt Univ, IMO, Div Chem, B-3590 Diepenbeek, Belgium. [Scholtens, B. J. R.; Quaedflieg, M. P.] DSM Xplore, NL-6160 MD Geleen, Netherlands. Victor.Litvinov@DSM.com; Guy.VandenMooter@pharm.kuleuven.be
URI: http://hdl.handle.net/1942/14311
DOI: 10.1021/mp300280k
ISI #: 000309314900014
ISSN: 1543-8384
Category: A1
Type: Journal Contribution
Validation: ecoom, 2013
Appears in Collections: Research publications

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