کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2083249 1545318 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evolution of a mini-scale biphasic dissolution model: Impact of model parameters on partitioning of dissolved API and modelling of in vivo-relevant kinetics
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Evolution of a mini-scale biphasic dissolution model: Impact of model parameters on partitioning of dissolved API and modelling of in vivo-relevant kinetics
چکیده انگلیسی

Biphasic dissolution models are proposed to have good predictive power for the in vivo absorption. The aim of this study was to improve our previously introduced mini-scale dissolution model to mimic in vivo situations more realistically and to increase the robustness of the experimental model.Six dissolved APIs (BCS II) were tested applying the improved mini-scale biphasic dissolution model (miBIdi-pH-II). The influence of experimental model parameters including various excipients, API concentrations, dual paddle and its rotation speed was investigated. The kinetics in the biphasic model was described applying a one- and four-compartment pharmacokinetic (PK) model.The improved biphasic dissolution model was robust related to differing APIs and excipient concentrations. The dual paddle guaranteed homogenous mixing in both phases; the optimal rotation speed was 25 and 75 rpm for the aqueous and the octanol phase, respectively. A one-compartment PK model adequately characterised the data of fully dissolved APIs. A four-compartment PK model best quantified dissolution, precipitation, and partitioning also of undissolved amounts due to realistic pH profiles.The improved dissolution model is a powerful tool for investigating the interplay between dissolution, precipitation and partitioning of various poorly soluble APIs (BCS II). In vivo-relevant PK parameters could be estimated applying respective PK models.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 105, August 2016, Pages 166–175
نویسندگان
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