Characterization and evaluation of a modified PVPA barrier in comparison to Caco-2 cell monolayers for combined dissolution and permeation testing.

Aim of this study was to implement a modified phospholipid vesicle-based permeation assay (PVPA) barrier as alternative to Caco-2 cell monolayers in a combined dissolution and permeation system for testing of solid dosage forms. Commercially available Transwell® inserts were coated with egg phospholipids (Lipoid E 80) and characterized by confocal Raman microscopy. The modified PVPA barrier was then evaluated in permeation studies with solutions of different drugs as well as in combined dissolution and permeation studies utilizing an immediate and an extended release tablet formulation.

Compound selection for development - is salt formation the ultimate answer? Experiences with an extended concept of the "100mg approach".

In order to select the best candidates for development, physicochemical criteria such as solubility, chemical and physical stability, hygroscopicity, and thermal characteristics need to be evaluated as early as possible and balanced against other important criteria such as pharmacology or pharmacokinetics. It could be shown, that our miniaturized pharmaceutical profiling concept ("100mg approach"), is capable to reliably identify potential development issues of drug candidates, which, therefore, can be approached early on. Salt formation is a well established strategy to improve unfavorable properties, in particular poor solubility.

Online monitoring of transepithelial electrical resistance (TEER) in an apparatus for combined dissolution and permeation testing.

The aim of this study was to evaluate a newly implemented feature for the online monitoring of transepithelial electrical resistance (TEER) in an apparatus for combined in vitro dissolution and permeation testing. In a first step, the course of TEER was analyzed simultaneously to the permeability of sodium fluorescein, and a time frame of cell monolayer integrity inside the apparatus of approximately 3h was found. In successive experiments cell monolayer integrity was challenged by application of EDTA (8, 6, 3 and 2 mM) in the apical compartment.

Automated measurement of permeation and dissolution of propranolol HCl tablets using sequential injection analysis.

Aim of this study was to automate sampling and quantification of the previously described apparatus for combined determination of dissolution and permeation through Caco-2 monolayer by means of sequential injection analysis (SIA). Native fluorescence of propranolol HCl in Krebs-Ringer buffer (KRB) was used for quantification. Sampling was done at three different locations within the apparatus at a high sampling frequency (approximately 60 h(-1)).

Permeability assessment for solid oral drug formulations based on Caco-2 monolayer in combination with a flow through dissolution cell.

The aim of our study was to develop an apparatus assessing in vitro permeation through Caco-2 monolayers of oral solid dosage forms as a possible tool to forecast in vivo performance. Therefore, flow through dissolution and permeation modules were connected by means of a stream splitter. Permeation was measured in a specially designed cell, dissolution took place in the apparatus 4, USP.

Pharmaceutical evaluation of early development candidates "the 100 mg-approach".

Early development candidates are often selected for pre-clinical and clinical development based primarily on pharmacological and toxicological data. In order to choose the best compounds from a biopharmaceutical point of view, physicochemical parameters such as solubility, dissolution rate, hygroscopicity, lipophilicity, pKa, stability, polymorphism and particle characteristics need to be evaluated as early as possible and above all with the highest accuracy. However, the low amounts of drug substance available in early development often compromise data quality, and therefore, hamper an early pharmaceutical assessment.