Abstract:
PURPOSE:The purpose of this study was (i) to develop glancing angle x-ray powder diffractometry (XRD) as a method for profiling phase transformations as a function of tablet depth; and (ii) to apply this technique to (a) study indomethacin crystallization during dissolution of partially amorphous indomethacin tablets and to (b) profile anhydrate --> hydrate transformations during dissolution of theophylline tablets. METHODS:The intrinsic dissolution rates of indomethacin and theophylline were determined after different pharmaceutical processing steps. Phase transformations during dissolution were evaluated by various techniques. Transformation in the bulk and on the tablet surface was characterized by conventional XRD and scanning electron microscopy, respectively. Glancing angle XRD enabled us to profile these transformations as a function of depth from the tablet surface. RESULTS:Pharmaceutical processing resulted in a decrease in crystallinity of both indomethacin and theophylline. When placed in contact with the dissolution medium, while indomethacin recrystallized, theophylline anhydrate rapidly converted to theophylline monohydrate. Due to intimate contact with the dissolution medium, drug transformation occurred to a greater extent at or near the tablet surface. Glancing angle XRD enabled us to depth profile the extent of phase transformations as a function of the distance from the tablet surface. The processed sample (both indomethacin and theophylline) transformed more rapidly than did the corresponding unprocessed drug. Several challenges associated with the glancing angle technique, that is, the effects of sorbed water, phase transformations during the experimental timescale, and the influence of phase transformation on penetration depth, were addressed. CONCLUSIONS:Increased solubility, and consequently dissolution rate, is one of the potential advantages of metastable phases. This advantage is negated if, during dissolution, the metastable to stable transformation rate > dissolution rate. Glancing angle XRD enabled us to quantify and thereby profile phase transformations as a function of compact depth. The technique has potential utility in monitoring surface reactions, both chemical decomposition and physical transformations, in pharmaceutical systems.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Debnath S,Predecki P,Suryanarayanan Rdoi
10.1023/b:pham.0000012163.89163.f8subject
Has Abstractpub_date
2004-01-01 00:00:00pages
149-59issue
1eissn
0724-8741issn
1573-904Xjournal_volume
21pub_type
杂志文章abstract:PURPOSE:To evaluate the effects of several buffers and excipients on the stability of glucagon during freeze-drying and storage as dried powder formulations. METHODS:The chemical and physical stability of glucagon in freeze-dried solid formulations was evaluated by a variety of techniques including mass spectrometry (...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0820-7
更新日期:2012-12-01 00:00:00
abstract:PURPOSE:The objective of this study was to investigate the possible influence of probenecid on morphine transport across the blood-brain barrier (BBB) in rats. METHODS:Microdialysis probes, calibrated using retrodialysis by drug, were placed into the striatum and jugular vein of seven Sprague-Dawley rats. Morphine was...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1023250900462
更新日期:2003-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-1869-5
更新日期:2016-05-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章
doi:10.1023/a:1016040825844
更新日期:1996-06-01 00:00:00
abstract:PURPOSE:There is evidence that cholesterol affects the ATPase and transport functions of P-glycoprotein (P-gp). To study the influence of cholesterol on P-gp in a well defined lipid environment, we reconstituted P-gp in egg phosphatidylcholine (PhC) and PhC/cholesterol proteoliposomes with negligible residual amounts o...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9326-0
更新日期:2007-11-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9420-3
更新日期:2008-03-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
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更新日期:2008-12-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2344-2
更新日期:2018-02-08 00:00:00
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pub_type: 杂志文章
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更新日期:2018-08-30 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2007-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s11095-012-0766-9
更新日期:2012-09-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2015-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s11095-015-1634-1
更新日期:2015-07-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011014629551
更新日期:2001-04-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2019-12-17 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016381215385
更新日期:1985-11-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/B:PHAM.0000019303.12086.d1
更新日期:2004-03-01 00:00:00
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更新日期:2005-07-01 00:00:00
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journal_title:Pharmaceutical research
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更新日期:2004-06-01 00:00:00
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更新日期:2000-08-01 00:00:00
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journal_title:Pharmaceutical research
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更新日期:2020-01-03 00:00:00
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pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章,已发布勘误
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更新日期:2018-09-05 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1025053115583
更新日期:2003-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015845306124
更新日期:1990-02-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2007-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:1992-12-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016081618149
更新日期:1996-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2008-04-01 00:00:00