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Budapest, Hungary

Balogh G.T.,Compound Profiling Laboratory | Muller J.,Budapest University of Technology and Economics | Konczol A.,Compound Profiling Laboratory
European Journal of Pharmaceutical Sciences

In the present study we validated a widely used, high-throughput in vitro permeability model (PAMPA) to be used at the early stage of drug discovery for the phospholipidosis (PLD) prediction of drug-like compounds. Regarding the mechanism of action of PLD, our pH-gradient PAMPA system is the first noncell based model to mimic one-way transport of cationic amphiphilic drugs (CADs) from cytosol to the lysosome. Moreover, due to the fact that PLD can mainly occur in lung, liver, brain, kidney and heart, we have used similar commercially available original tissue-derived lipid fractions (heart, liver, brain), and in the case mimicking membrane of kidney and lung tissue we prepared tissue-mimetic artificial lipid mixtures in house. Metabolism of a drug can change the degree of PLD depending on the physicochemical properties of metabolites and the rate of metabolism. Our data from 57 drugs and 4 metabolites of earlier and 2 metabolites of newly recognized outliers (phenacetin and bupropion) using our pH-gradient PAMPA system show a good correlation with in vivo PLD data. Moreover, predictive ability of our best system, the lung specific pH-gradient PAMPA model was significantly better than widely used in silico models and it was also slightly better than that of the known noncell based models on our selection of compounds. Our pH-gradient PAMPA systems therefore offer mechanistically alternative, accurate and cost-effective screening tools for the early prediction of PLD potential of drug-like compounds. © 2013 Elsevier B.V. All rights reserved. Source

Borbas E.,Budapest University of Technology and Economics | Balogh A.,Budapest University of Technology and Economics | Bocz K.,Budapest University of Technology and Economics | Muller J.,Budapest University of Technology and Economics | And 9 more authors.
International Journal of Pharmaceutics

Abstract Since it is a well-known fact that among the newly discovered active pharmaceutical ingredients the number of poorly water soluble candidates is continually increasing, dissolution enhancement of poorly water soluble drugs has become one of the central challenges of pharmaceutical studies. So far the preclinical studies have been mainly focused on formulation methods to enhance the dissolution of active compounds, in many cases disregarding the fact that the formulation matrix not only affects dissolution but also has an effect on the transport through biological membranes, changing permeation of the drug molecules. The aim of this study was to test an electrospun cyclodextrin-based formulation of aripiprazole with the novel μFlux apparatus, which monitors permeation together with dissolution, and by this means better in vitro-in vivo correlation is achieved. It was evinced that a cyclodextrin-based electrospun formulation of aripiprazole has the potential to ensure fast drug delivery through the oral mucosa owing to the ultrafast dissolution of the drug from the formulation and the enhanced flux across membranes as shown by the result of the novel in vitro dissolution and permeation test. © 2015 Elsevier B.V. Source

Nemeth T.,Budapest University of Technology and Economics | Kormos A.,Budapest University of Technology and Economics | Toth T.,Budapest University of Technology and Economics | Balogh G.T.,Compound Profiling Laboratory | Huszthy P.,Budapest University of Technology and Economics
Monatshefte fur Chemie

Abstract: The synthesis of a new acridono-18-crown-6 ether type sensor has been carried out starting from commercially available and relatively cheap materials. The cation recognition ability of the new ligand and also a reported analog thereof toward various metal ions was studied in acetonitrile by UV/Vis spectroscopy. Our studies revealed the selective binding of Pb2+ ions by the latter ligand. Based on our calculations, we suggest the formation of a complex with 1:1 ligand to metal ion ratio. Graphical abstract: [Figure not available: see fulltext.] © 2015 Springer-Verlag Wien Source

Konczol A.,Compound Profiling Laboratory | Muller J.,Compound Profiling Laboratory | Muller J.,Budapest University of Technology and Economics | Foldes E.,Budapest University of Technology and Economics | And 4 more authors.
Journal of Natural Products

While numerous natural products (NPs) possess activity on central nervous system (CNS) targets, there has been no analytical approach to effectively identify compounds with high brain penetration potential in complex mixtures at the early stage of drug discovery. To overcome this issue, the performance of an in vitro parallel artificial membrane permeability assay for the blood-brain barrier (PAMPA-BBB) for natural products and for plant extracts has been validated and characterized. It was found that the PAMPA-BBB assay preserves its predictive power in the case of natural products and provides high phytochemical selectivity, which enables its use as a unique filtering tool in terms of selecting brain-penetrable compounds from plant extracts. Moreover, the present study has demonstrated that simple modifications in the assay design allow the direct use of PAMPA-BBB filtered samples in a dereplication process, as performed by NMR and LC-MS. The applicability of this procedure was demonstrated using extracts prepared from Tanacetum parthenium, Vinca major, Salvia officinalis, and Corydalis cava, representing different types of chemical diversity and complexity. Thus, the proposed protocol represents a potentially valuable strategy in the NP-based CNS drug discovery environment with a high-throughput screening platform. © 2013 The American Chemical Society and American Society of Pharmacognosy. Source

Nemeth T.,Budapest University of Technology and Economics | Levai S.,Compound Profiling Laboratory | Kormos A.,Budapest University of Technology and Economics | Kupai J.,Budapest University of Technology and Economics | And 3 more authors.

The enantiomeric separation ability of the newly prepared chiral stationary phases containing acridino-18-crown-6 ether selectors was studied by high-performance liquid chromatography (HPLC). The chiral stationary phases separated the enantiomers of selected protonated primary aralkylamines efficiently. The best results were found for the separation of the mixtures of enantiomers of NO2-PEA. Chirality 26:651-654, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc. Source

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