کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2503460 1557426 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Encapsulation of poorly soluble basic drugs into enteric microparticles: A novel approach to enhance their oral bioavailability
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Encapsulation of poorly soluble basic drugs into enteric microparticles: A novel approach to enhance their oral bioavailability
چکیده انگلیسی

Poorly water soluble basic drugs are very sensitive to pH changes and following dissolution in the acidic stomach environment tend to precipitate upon gastric emptying, which leads to compromised or erratic oral bioavailability. In this work, we show that the oral bioavailability of a model poorly soluble basic drug (cinnarizine) can be improved by drug encapsulation within highly pH-responsive microparticles (Eudragit L). The latter was prepared by emulsion solvent evaporation which yielded discrete spherical microparticles (diameter of 56.4 ± 6.8 μm and a span of 1.2 ± 0.3). These Eudragit L (dissolution threshold pH 6.0) microparticles are expected to dissolve and release their drug load at intestinal conditions. Thus, the enteric microparticles inhibited the in vitro release of drug under gastric conditions, despite high cinnarizine solubility in the acidic medium. At intestinal conditions, the particles dissolved rapidly and released the drug which precipitated out in the dissolution vessel. In contrast, cinnarizine powder showed rapid drug dissolution at low pH, followed by precipitation upon pH change. Oral dosing in rats resulted in a greater than double bioavailability of Eudragit L microparticles compared to the drug powder suspension, although Cmax and Tmax were similar. The higher bioavailability with microparticles contradicts the in vitro results. Such an example highlights that although in vitro results are an indispensable tool for formulation development, an early in vivo assessment of formulation behaviour can provide better prediction for oral bioavailability.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 416, Issue 1, 15 September 2011, Pages 55–60
نویسندگان
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