کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485847 | 1114368 | 2012 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A Formulation Strategy for Gamma Secretase Inhibitor ELND006, a BCS Class II Compound: Development of a Nanosuspension Formulation with Improved Oral Bioavailability and Reduced Food Effects in Dogs
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کلمات کلیدی
Food effects - اثرات غذاییDissolution - انحلال Solubility - انحلال پذیریParticle size - اندازه ذراتAlzheimer's disease - بیماری آلزایمرOral drug delivery - تحویل داروی خوراکیBiopharmaceutics Classification System (BCS) - سیستم طبقه بندی بیولوژیک (BCS)Pharmacokinetics - فارماکوکینتیکBioavailability - فراهم زیستیGamma secretase inhibitor - مهار کننده گاما اسید معدهCrystallinity - کریستالی شدن یا تبلور
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A Formulation Strategy for Gamma Secretase Inhibitor ELND006, a BCS Class II Compound: Development of a Nanosuspension Formulation with Improved Oral Bioavailability and Reduced Food Effects in Dogs A Formulation Strategy for Gamma Secretase Inhibitor ELND006, a BCS Class II Compound: Development of a Nanosuspension Formulation with Improved Oral Bioavailability and Reduced Food Effects in Dogs](/preview/png/2485847.png)
چکیده انگلیسی
ELND006 is a novel gamma secretase inhibitor previously under investigation for the oral treatment of Alzheimer's disease. ELND006 shows poor solubility and has moderate to high permeability, suggesting it is a Biopharmaceutics Classification System Class II compound. The poor absolute oral bioavailability of the compound in fasted dogs (F â¼11%) is attributed to poor aqueous solubility. In addition, inhibiting amyloid precursor protein but not Notch cleavage is an important goal for gamma secretase inhibitors; therefore, significant variation in bioavailability resulting from food consumption is a potential liability for this class of compounds. The objective of the present study was to determine if an ELND006 nanocrystalline formulation would offer improved and predictable pharmacokinetics. ELND006 was formulated as a nanosuspension with a mean particle size of less than 200Â nm, which was stable in particle size and crystallinity for over 1Â year. In addition, ELND006 nanosuspension exhibited rapid dissolution in comparison with reference active pharmaceutical ingredient (API). The in vivo performance of the ELND006 nanosuspension was tested in fed and fasted beagle dogs and compared with a gelatin capsule containing reference API. The results show that nanosizing ELND006 profoundly improved the oral bioavailability and virtually eliminated variation resulting from food intake. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 4, April 2012, Pages 1462-1474
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 4, April 2012, Pages 1462-1474
نویسندگان
Kevin Quinn, Rampurna Prasad Gullapalli, Elaine Merisko-liversidge, Erich Goldbach, Angelina Wong, Gary G. Liversidge, Wherly Hoffman, John-michael Sauer, John Bullock, George Tonn,