کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8513786 1556500 2017 38 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Real-Time Analysis of Tenofovir Release Kinetics Using Quantitative Phosphorus (31P) Nuclear Magnetic Resonance Spectroscopy
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Real-Time Analysis of Tenofovir Release Kinetics Using Quantitative Phosphorus (31P) Nuclear Magnetic Resonance Spectroscopy
چکیده انگلیسی
The dialysis method is classically used for drug separation before analysis, but does not provide direct and real-time drug quantification and has limitations affecting the dialysis rate. In this study, a phosphorus nuclear magnetic resonance (31P-qNMR) method is developed for the real-time quantification of therapeutic molecules in vitro. The release kinetics of model drug, tenofovir (anti-HIV microbicide), was analyzed in vaginal fluid simulant (VFS), seminal fluid simulant (SFS), and human plasma (HP) from chitosan nanofibers (size ∼100-200 nm) using the NMR (direct) method and compared with dialysis/UV-Vis (indirect) method. The assay was linear in VFS/SFS (0.20-5.0 mM), HP (0.30-5.0 mM of drug concentration range) and specific no drug 31P-qNMR chemical shift [∼15 ppm] interference with formulation/media components. Limit of detection values were 0.075/0.10/0.20 mM, whereas limit of quantification values were 0.20/0.20/0.30 mM in VFS/SFS/HP, respectively. The method was robust, precise (%RSE <2%), and accurate (%mean recovery 90%-110%). After 12 h, ∼77%/72%/70% wt/wt of tenofovir release was observed with direct, compared to ∼47%/52%/52% wt/wt by indirect method in VFS/SFS/HP, respectively. Approximately 20% decrease in %drug release observed with dialysis method suggested an interference with drug transport process due to the dialysis membrane and the Gibbs-Donnan effect. Overall, 31P-qNMR provides more accurate, real-time, and direct drug quantification for effective in vitro-in vivo correlation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 10, October 2017, Pages 3005-3015
نویسندگان
, , , , ,