Flow-Through Cell Method and IVIVR for Poorly Soluble Drugs

Abstract

The percentage of poorly soluble compounds in drug discovery and development increases steadily. A variety of possibilities exists for increasing solubility and bioavailability; among them is the formation of salts. For the characterization of poorly soluble active pharmaceutical ingredients (API), it is necessary to develop appropriate analytical methods to determine relevant physicochemical properties. One important physicochemical parameter is the dissolution rate. As the flow-through cell (FTC) offers various advantages, such as operating with pH gradients and in sink conditions or applying unlimited amount of media, the FTC is particularly suitable for poorly soluble compounds. When developing an FTC method it is important to consider the physiological circumstances. By choosing the appropriate conditions for media, volume, flow rate, and so forth, it is possible to predict in vivo behavior. The focus of this work was to develop a small-scale FTC method for poorly soluble compounds designed for determining dissolution kinetics in the early development phase, where only limited amount of drug is available. The predictive power of the presented system could be demonstrated by an in vitro-in vivo relationship (IVIVR) study.

Comparative in Vitro Dissolution Study on Metformin Market Products Using Different Dissolution Apparatuses

“…Although the Flow through the cell (FTC) became an official USP method since 1995 (USP Apparatus IV) [8], in vitro dissolution studies using this apparatus under different operational conditions and/or features are few in literature [5,[9][10][11][12][13][14][15][16][17]. Our previous studies using the FTC proved that we should optimize the in vitro dissolution conditions for the finished product or during the preparation of different formulations to achieve accurate and reproducible results and to detect the effect of minor formulation changes upon storage [18].…”

The Flow-Through Cell as an In Vitro Dissolution Discriminative Tool for Evaluation of Gliclazide Solid Dispersions

“…It is a prerequisite test required before carrying out bioavailability or bioequivalence studies (Wähling et al, 2011). Although the Flow through cell (FTC) became an official USP method since 1995 (USP App.…”

“…Although the Flow through cell (FTC) became an official USP method since 1995 (USP App. 4) (Wähling et al, 2011), in vitro dissolution studies using this apparatus under different operational conditions and/or features are very few in literature (Emara et al, 2014a;Emara et al, 2014b;Emara et al, 2013;Emara et al, 2009;Krämer and Stippler, 2005;Beyssac and Lavigne, 2005;Fotaki and Reppas, 2005;Bhattachar et al, 2002;Emara et al, 2000). Our previous studies using the FTC proved that we should optimize the in vitro dissolution conditions for the finished product or during the preparation of different formulations to achieve accurate and reproducible results and to detect the effect of minor formulation changes upon storage.…”

Characterization of Multi-Sourced Diclofenac Sodium Extended-Release Tablet Dissolution Profiles: A New Approach to Establish an In vitro-In vivo Correlation Based on Multiple Integral Response Surface

“…DE is chosen for parameter derivation not only for few usage restrictions (the only restriction to be considered is the time range applied for the calculation of DE), but also for its relation with IVIVC or in vitro-in vivo relationships (IVIVR) [9].…”