کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487774 | 1114431 | 2007 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Screening Method to Identify Preclinical Liquid and SemiâSolid Formulations for low Solubility Compounds: Miniaturization and Automation of Solvent Casting and Dissolution Testing
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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
We have developed an efficient screening method to identify liquid and semisolid formulations for lowâsolubility compounds. The method is most suitable for identifying dosing vehicles for compounds in lead optimization, where compound supply is limited and longâterm stability is not a requirement. Dilute compound and excipient stock solutions are prepared in organic solvent and then dispensed and mixed in 96âwell plates. The solvent is removed in a vacuum centrifuge evaporator, leaving neat formulation (e.g., 10-40 µg compound, 0.4 mg excipient) at the bottom of each well. After an aging step, an aqueous dilution medium is added and the plates are incubated (agitation by orbital shaking). The diluted formulations are then filtered and analyzed by ultraviolet (UV) absorbance or highâperformance liquid chromatography (HPLC). To illustrate the method, two compounds (aqueous solubility â¤1 µg/mL) were combined with eight solubilizing excipients, at four drugâloading levels (25, 50, 75, and 100 mg/g) and three incubation times (0.5, 2, and 24 h). This allowed identification of the excipients and loading levels, which generated the highest and most stable kinetic solubility upon dilution. The peak kinetic solubility was strongly correlated with the equilibrium solubility. Application of the method to screening compound/surfactant/oil formulations is also presented.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 6, June 2007, Pages 1548-1563
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 6, June 2007, Pages 1548-1563
نویسندگان
Paul Mansky, WeiâGuo Dai, Shu Li, Crystal PollockâDove, Klaus Daehne, Liang Dong, Gary Eichenbaum,