An in vitro–in silico–in vivo approach to predicting the oral pharmacokinetic profile of salts of weak acids: Case example dantrolene

Kambayashi, Atsushi; Dressman, Jennifer B.

doi:10.1016/j.ejpb.2012.12.001

Cited by 42 publications

(33 citation statements)

References 28 publications

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“…The experimental condition like fluid transfer rate and dissolution media could be modified to more biorelevant conditions for better prediction. Especially for dissolution media, several different dissolution media like bicarbonate and FaSSIF buffers have been tested to predict better in vivo dissolution of oral products (Do et al, 2011;Fei et al, 2013;Kambayashi and Dressman, 2013; Krieg et al, 2014;Taupitz et al, 2013). The implementation of biorelevant media into mGIS could improve the prediction of in vivo dissolution.…”

Section: Discussionmentioning

confidence: 99%

In vitro dissolution methodology, mini-Gastrointestinal Simulator (mGIS), predicts better in vivo dissolution of a weak base drug, dasatinib

Tsume

Takeuchi

Matsui

et al. 2015

European Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 99%

In vitro dissolution methodology, mini-Gastrointestinal Simulator (mGIS), predicts better in vivo dissolution of a weak base drug, dasatinib

Tsume

Takeuchi

Matsui

et al. 2015

European Journal of Pharmaceutical Sciences

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“…It is hard to predict the mean precipitation time because it depends on the formulation and physicochemical properties of drug compound. The range of precipitation time, 15–75 min, has been calculated from the various experiments (Carlert et al, 2010; Kambayashi and Dressman, 2013; Lindfors et al, 2008). The mean precipitation time of 900 s (15 min) was chosen and was used it with a coefficient of variation for virtual trials.…”

Section: Methodsmentioning

confidence: 99%

The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC

Tsume

Mudie

Langguth

et al. 2014

European Journal of Pharmaceutical Sciences

279

169

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The Biopharmaceutics Classification System (BCS) has found widespread utility in drug discovery, product development and drug product regulatory sciences. The classification scheme captures the two most significant factors influencing oral drug absorption; solubility and intestinal permeability and it has proven to be a very useful and a widely accepted starting point for drug product development and drug product regulation. The mechanistic base of the BCS approach has, no doubt, contributed to its wide spread acceptance and utility. Nevertheless, underneath the simplicity of BCS are many detailed complexities, both in vitro and in vivo which must be evaluated and investigated for any given drug and drug product. In this manuscript we propose a simple extension of the BCS classes to include subspecification of acid (a), base (b) and neutral (c) for classes II and IV. Sub-classification for Classes I and III (high solubility drugs as currently defined) is generally not needed except perhaps in border line solubility cases. It is well known that the , pKa physical property of a drug (API) has a significant impact on the aqueous solubility dissolution of drug from the drug product both in vitro and in vivo for BCS Class II and IV acids and bases, and is the basis, we propose for a sub-classification extension of the original BCS classification. This BCS sub-classification is particularly important for in vivo predictive dissolution methodology development due to the complex and variable in vivo environment in the gastrointestinal tract, with its changing pH, buffer capacity, luminal volume, surfactant luminal conditions, permeability profile along the gastrointestinal tract and variable transit and fasted and fed states. We believe this sub-classification is a step toward developing a more science-based mechanistic in vivo predictive dissolution (IPD) methodology. Such a dissolution methodology can be used by development scientists to assess the likelihood of a formulation and dosage form functioning as desired in humans, can be optimized along with parallel human pharmacokinetic studies to set a dissolution methodology for Quality by Design (QbD) and in vitro–in vivo correlations (IVIVC) and ultimately can be used as a basis for a dissolution standard that will ensure continued in vivo product performance.

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“…Nevertheless, it is not clear whether RyR2 modulators, comprising a class of drugs, would be beneficial in the treatment of VF or if the effect is specific to dantrolene alone. More importantly, dantrolene is highly lipophilic and poorly water‐soluble, limiting its preparation and administration . Azumolene is a dantrolene analog that is 30 times more soluble in water and may be more useful clinically .…”

Section: Introductionmentioning

confidence: 99%

Essential role of ryanodine receptor 2 phosphorylation in the effect of azumolene on ventricular arrhythmia vulnerability in a rabbit heart model

Azam

Lai

et al. 2018

Cardiovasc electrophysiol

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show abstract

An in vitro–in silico–in vivo approach to predicting the oral pharmacokinetic profile of salts of weak acids: Case example dantrolene

Cited by 42 publications

References 28 publications

In vitro dissolution methodology, mini-Gastrointestinal Simulator (mGIS), predicts better in vivo dissolution of a weak base drug, dasatinib

In vitro dissolution methodology, mini-Gastrointestinal Simulator (mGIS), predicts better in vivo dissolution of a weak base drug, dasatinib

The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC

Essential role of ryanodine receptor 2 phosphorylation in the effect of azumolene on ventricular arrhythmia vulnerability in a rabbit heart model

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