期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 102, 期 6, 页码 1924-1935出版社
WILEY-BLACKWELL
DOI: 10.1002/jps.23539
关键词
crystallization; interaction; polymers; precipitation; solid dispersion
Our major goals were to understand the mechanism of dipyridamole (DPD) precipitation inhibition in the presence of polymers and to correlate the polymers-mediated precipitation inhibition in solution to the amorphous stabilization in the solid state. A continuous UV spectrophotometer was used to monitor the DPD concentration with time in the absence and presence of different polymers. Six polymers: PVP K90, hydroxypropylmethylcellulose (HPMC), Eudragit E100, Eudragit S100, Eudragit L100, and PEG 8000 were screened at different drug-to-monomer ratios. Solid dispersions were characterized by X-ray powder diffraction and modulated differential scanning calorimetry, whereas infrared (IR) and Raman were used to investigate the possible drugpolymer interactions. Eudragit E100 and HPMC were found to delay both DPD precipitation initiation time and precipitation rates. Eudragit S100 delayed only the precipitation initiation time and PVP K90 decreased only the precipitation rates. In solid state, Eudragit S100, PVP K90, HPMC, and Eudragit L100 were effective stabilizers of the DPD solid dispersion. Eudragit S100 was found to be most effective DPD-stabilizing polymer. The IR and Raman spectra of the solid dispersion of Eudragit S100 and HPMC showed peak shift, indicating drugpolymer molecular interactions. It is concluded that the drugpolymer interaction plays a significant role in precipitation inhibition and amorphous stabilization. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:19241935, 2013
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