کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486182 | 1114377 | 2011 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Drug release from HPMC matrices in milk and fatârich emulsions
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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
“Biorelevant” media for the fed stomach, including fat emulsions, are routinely used during in vitro testing of solid dosage forms. However, their complexity undoubtedly creates difficulties in identifying factors which affect drug release. Here, we show fats can directly influence drug release from hydroxypropyl methylcellulose (HPMC; Methocel K4M) matrices which are often subjected to biorelevant testing. Model fat systems included milk (0.1%-3.5% fat) and the parenteral emulsion Intralipid® (20%-30% fat). The matrix showed good extendedârelease properties for at least 12âh in these media (USPâ1/USPâ4), but at the highest fat concentration, release was retarded and shifted towards zeroâorder release. Confocal imaging studies using a waterâsoluble (fluorescein) and fatâsoluble (Nile red) fluorophore provided evidence of phase separation of Intralipid® at the surface of the emerging gel. Combined magnetic resonance imaging-USPâ4 drug release testing provided further evidence for deposition of fat on the tablets. We propose that the aqueous portion of the emulsion is removed by the hydrating matrix, causing coalescence and deposition of a fat layer at the surface, and these deposits cause slower drug release by reducing the matrix surface area available for release. Therefore, there is a risk of a direct interaction between fat emulsions and HPMC tablets, with resultant effects on drug release in vitro. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:4823-4835, 2011
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 11, November 2011, Pages 4823-4835
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 11, November 2011, Pages 4823-4835
نویسندگان
Hywel D. Williams, Kevin P. Nott, David A. Barrett, Rob Ward, Ian J. Hardy, Colin D. Melia,