期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 98, 期 12, 页码 4724-4737出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.21782
关键词
solid dispersion; spray drying; globules; solvent effect; relaxation; glass transition temperature; viscosity; evaporation rate; dissolution rate
资金
- School of Pharmacy/University of London
The use of solid dispersions for oral dosage forms can increase the dissolution rate of poorly soluble drugs. Spray drying is one process that can be used to prepare solid dispersions. Spray dried solid dispersions of griseofulvin, poly[N-(2-hydroxypropyl)methacrylate] (PHPMA) and polyvinylpyrrolidone (PVP) were prepared from acetone and water. When methanol was substituted for water, the morphology, stability and dissolution properties of the solid dispersion changed dramatically. The glass transition temperature for the ternary solid dispersion (GF, PHPMA, and PVP) shifted from 83 degrees C (acetone/water) to 103 degrees C for the acetone/methanol system. These differences in the dispersions are thought to derive from conformational variations of the polymers in solution prior to spray drying. Both PHPMA and PVP formed globules in solution of a size range between 16 and 33 nm. The effect of drug and polymer concentration in solution (before spray drying) on the properties of the solid dispersion was studied. It was found that solid dispersions that were prepared using lower concentrations of drug and polymers in solutions resulted in the formation of particles that display a lower relaxation rate. This result supports the hypothesis that the polymer conformation may significantly change the properties of the solid dispersion. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4724-4737, 2009
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