Preparation of budesonide- and indomethacin-hydroxypropyl-β-cyclodextrin (HPBCD) complexes using a single-step, organic-solvent-free supercritical fluid process

被引:90
作者
Bandi, N
Wei, W
Roberts, CB
Kotra, LP
Kompella, UB
机构
[1] Univ Nebraska, Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA
[2] Univ Toronto, Dept Chem, Toronto, ON M5S 2S2, Canada
[3] Auburn Univ, Dept Chem Engn, Auburn, AL 36849 USA
关键词
budesonide; carbon dioxide; complexation; cyclodextrin; indomethacin; supercritical fluid;
D O I
10.1016/j.ejps.2004.06.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The purpose of this study was to determine whether budesonide- and indomethacin-hydroxypropyl-beta-cyclodextrin (HPBCD) complexes could be formed using a supercritical fluid (SCF) process. The process involved the exposure of drug-HPBCD mixtures to supercritical carbon dioxide (SC CO2). The ability of the SCF process to form complexes was assessed by determining drug dissolution, drug crystallinity, and drug-excipient interactions. Drug dissolution was assessed using a HPLC assay. Crystallinity was assessed using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). Drug-excipient interactions were characterized using Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) was used to determine any morphological changes. SC CO2 process did not alter the dissolution rate of pure drugs but resulted in two- and three-fold higher dissolution rates for budesonide- and indomethacin-HPBCD mixtures, respectively. SCF-processed mixtures exhibited a disappearance of the crystalline peaks of the drugs (PXRD), a partial or complete absence of the melting endotherm of the drugs (DSC), and a shift in the C=O stretching of the carboxyl groups of the drugs (FTIR), consistent with the loss of drug crystallinity and formation of intermolecular bonds with HPBCD. SEM indicated no discernible drug crystals upon physical mixing with or without SCF processing. Thus, budesonide- and indomethacin-HPBCD complexes with enhanced dissolution rate can be formed using a single-step, organic solvent-free SC CO2 process. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:159 / 168
页数:10
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