کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486867 | 1114396 | 2008 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Rapid Throughput Screening of Apparent KSP values for Weakly Basic Drugs Using 96-Well Format
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کلمات کلیدی
Dissolution - انحلال Solubility - انحلال پذیریThermodynamics - ترمودینامیکSolvation - حل کردنPhysical characterization - خصوصیات فیزیکیPhysiochemical properties - خواص فیزیکی و شیمیاییCounter ion - ضد یونExcipients - عضلاتFormulation - فرمولاسیونHigh throughput technologies - فن آوری های پیشرفتهSolubility product - محصول حلالیتPreformulation - پیش فرآیند
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
A rapid-throughput screening assay was developed to estimate the salt solubility parameter, KSP, with a minimal quantity of drug. This assay allows for early evaluation of salt limited solubility with a large number of counter-ions and biologically promising drug leads. Drugs dissolved (typically 10 mM) in DMSO are robotically distributed to a 96-well plate. DMSO is evaporated, and drugs are equilibrated with various acids at different concentrations (typically <1 M) to yield final total drug concentrations around 2.5 mM. The plate is checked for precipitation. Filtrates from only those precipitated wells were subjected to rapid gradient HPLC analysis. An iterative procedure is employed to calculate all species concentrations based on mass and charge balance equations. The apparent KSP values assuming 1:1 stoichiometry are determined from counter-ion and ionized drug activities. A correlation coefficient >0.975 for eight drugs totaling 16 salts is reported. Intra-day and inter-day reproducibility was <10%. Conventional apparent KSP measurements were translated to 96-well format for increased throughput and minimal drug consumption (typically 10 mg) to evaluate at least eight different counter-ions. Although the current protocol estimates KSP from 10â3 to 10â7 M, the dynamic range of the assay could be expanded by adjusting drug and counter-ion concentrations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 6, June 2008, Pages 2080-2090
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 6, June 2008, Pages 2080-2090
نویسندگان
Jeremy Guo, Paul A. Elzinga, Michael J. Hageman, James N. Herron,