کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2485926 1114371 2012 23 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Solution-Mediated Phase Transformation: Significance During Dissolution and Implications for Bioavailability
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Solution-Mediated Phase Transformation: Significance During Dissolution and Implications for Bioavailability
چکیده انگلیسی

ABSTRACT:Solubility improvement of poorly soluble drug compounds is a key approach to ensuring the successful development of many new drugs. Methods used to improve the solubility of drug compounds include forming a salt, cocrystal, or amorphous solid. These methods of improving solubility can often lead to a phenomenon called solution-mediated phase transformation, a phase change that is facilitated through exposure to solution. Solution-mediated phase transformation occurs in three steps: dissolution to create a supersaturated solution followed by nucleation of less soluble phase and the growth of that phase. When the growth of the less soluble phase occurs on the surface of the metastable solid, this phenomenon can cause a marked decrease in dissolution rate during in vitro dissolution evaluation, and ultimately in vivo. Therefore, transformation to a less soluble solid during dissolution is an important aspect to consider when evaluating approaches to increase the solubility of a poorly soluble drug. Identification of solution-mediated phase transformation during dissolution is reviewed for powder dissolution, rotating disk method, and channel flow-through apparatus. Types of solution-mediated phase transformation are described in this report, including those involving salts, polymorphs, amorphous solids, and cocrystals. Many experimental examples are provided. Evidence of potential solution-mediated phase transformation in vivo is discussed to better understand the relationship between in vitro dissolution evaluation and in vivo performance.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 9, September 2012, Pages 2996–3018
نویسندگان
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