Molekuláris tulajdonságok és membrántranszport = Molecular properties and membrane transport
Bibliographic record
Abstract
Legfontosabb eredmenye, hogy kifejlesztettunk egy olyan micro-plate alapu in vitro, nagy ateresztőkepessegű permeabilitasi modellt, amely kepes a vegyuletek bőron keresztuli felszivodasat előre jelezni, ezaltal alkalmas a felfedező gyogyszerkutatasban a transzdermalis gyogyszerbevitelre szant vegyuletek kivalasztasara. Az u.n. „skin PAMPA” modell kidolgozasakor optimaltuk a membran osszetetelet, a hidratacio idejet es modjat, az inkubacio kiserleti korulmenyeit. A termeszetes bőralkoto ceramidok modellbeli helyettesitesere szintetizaltunk funkcioban es tulajdonsagokban hasonlo, de olcson előallithato hosszu szenlancu borkősavdiamidokat (certramidok). A modszert osszesen 38 elterő szerkezetű vegyulet felhasznalasaval validaltuk, prediktivitasat human bőr penetracios adatokkal valo osszehasonlitassal igazoltuk. A kidolgozott modszer standardizalt, jol reprodukalhato, robosztus es koltseghatekony eljaras. Szisztematikus vizsgalatok alapjan megallapitottuk az ionizalhato vegyuletek oldhatosag-pH fuggeset leiro Henderson-Hasselbalch egyenlet evenyesseget es korlatait. Vizsgaltuk a mikronizalas es nanonizalas hatasat az egyensulyi oldhatosagra tobb gyogyszeranyagon. Ramutattunk polimorfok egyensulyi oldhatosag mereseinek korlataira. Kidolgoztuk az egyensulyi oldhatosag meghatarozas helyes gyakorlatanak iranyelveit. Eredmenyeinket 6 megjelent es 2 megjelenes alatt levő publikacioban tettuk kozze. | As the most important novelty of this research, a high throughput microplate based in vitro permeability model has been developed for the prediction of human skin penetration that is suitable for pharmaceutical, cosmetic and chemical industry. The optimization of membrane composition and hydration and the determination of experimental parameters resulted in the so called “skin PAMPA” model. As ceramides were not suitable for usage in HT method, structural and chemical analogues, long chain tartaric acid diamides (certramides) have been synthesized and applied in the membrane. The model has been tested and validated using 38 structurally diverse compounds and its performance has been proved in correlation studies against 3 different human skin permeability databases, so it is a standardized, reproducible, robust and cost-effective system. The validity and limitations of Henderson-Hasselbalch equation describing the solubility-pH profile of ionizable compounds has been determined in a systematic study. The effect of micronization and nanonization on equilibrium solubility has been investigated on several different drug compounds. The limitations of equilibrium solubility determination of polymorphs have also been studied and the guidelines of equilibrium solubility determination have been established. Our results have been published in 6 peer-reviewed journals and two more paper is in the process of publication.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".