کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487498 | 1114419 | 2008 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Rapid Throughput Solubility Screening Method for BCS Class II Drugs in Animal GI Fluids and Simulated Human GI Fluids Using a 96âwell Format
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
A rapid solubilityâscreening assay was developed with a focus on Biopharmaceutic Classification Scheme (BCS) class II drug solubility in animal and simulated human gastrointestinal (GI) fluids. The assay enables biologically promising drug leads to be evaluated for solubility limitations earlier in the drug development process, minimizes GI fluid needs, and produces in vitro solubility information with potential in vivo implications. A number of BCS II drugs were dissolved in DMSO at â¼40 mM, and robotically distributed to a 96âwell plate. The DMSO was evaporated and drugs were equilibrated with selected GI fluids, both fed and fasted states. After equilibration, precipitated wells were subjected to HPLC analysis. A spreadsheet calculated solubility automatically from HPLC output. Intraâday, interâday, and interâplate reproducibility were within 15% RSTD for the tested drugs with the primary source of variability being injection precision of our injector system. The reported solubility from screening assays was well correlated with literature data (r2â=â0.80) with a slope of 0.86 and (r2â=â0.99) with a slope of 0.89. This screening assay converts conventional solubility measurements to a 96âwell format for increased throughput (>12 samples/h), reduces fluid needs, and minimizes drug consumption. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 97:1427-1442, 2008
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 4, April 2008, Pages 1427-1442
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 4, April 2008, Pages 1427-1442
نویسندگان
Jeremy Guo, Paul A. Elzinga, Michael.J. Hageman, James N. Herron,