دانلود کتاب خارجی - دانلود رایگان کتاب لاتین PDF علمی

تعداد نتایج: 664

Das keltische Amulett

Historischer Roman | Die große Schottland-Saga: Die Dalriada...

By Jules Watson
Publisher: dotbooks, 2022-06-14
Pages: 861
Language: de
ISBN_13:9783986902384
ISBN_10:3986902384
Subject: Fiction

AFTER LIFE

A Soul's Journey of Life, Death and Beyond

جزئیات و درخواست

By Claire Swinney
Publisher: First Edition Design Pub., 2015-09-16
Pages: 144
Language: en
ISBN_13:9781506900230
ISBN_10:1506900232
Subject: Body, Mind & Spirit

The Raven Queen

A Novel

جزئیات و درخواست

By Jules Watson
Publisher: Spectra, 2011-02-22
Pages: 546
Language: en
ISBN_13:9780345524867
ISBN_10:0345524861
Subject: Fiction

Song of the North

جزئیات و درخواست

By Jules Watson
Publisher: Abrams, 2008-01-10
Pages: 418
Language: en
ISBN_13:9781468301359
ISBN_10:1468301357
Subject: Fiction

The Swan Maiden

A Novel

جزئیات و درخواست

By Jules Watson
Publisher: Bantam, 2009-02-24
Pages: 562
Language: en
ISBN_13:9780553906301
ISBN_10:0553906305
Subject: Fiction

The Mulkeys of America

جزئیات و درخواست

By Philip Mulkey Hunt
1982
Pages: 954
Language: en
OTHER:WISC:89069671881

Cheryl Cole

Her Story - The Unauthorized Biography

جزئیات و درخواست

By Gerard Sanderson
Publisher: Michael O'Mara Books, 2010-08-20
Pages: 241
Language: en
ISBN_13:9781843175148
ISBN_10:1843175142
Subject: Biography & Autobiography

Catalog ...

جزئیات و درخواست

By Randolph-Macon Woman's College
1935
Pages: 134
Language: en
OTHER:UIUC:30112111433329

The Nature Oracle

30 Cards with Guidebook

جزئیات و درخواست

By Claire Swinney
2024-01-15
Language: en
ISBN_10:0645673927
ISBN_13:9780645673920
Subject: Body, Mind & Spirit

Prediction of biological membrane penetration of poorly soluble drugs using surface activity profiling

$Since combinatorial chemistry and high throughput screening have become a common technique in the drug discovery phase the number of compounds being considered has increased frequently. These structures are often characterized by high molecular weight, high lipophilicity and low solubility in aqueous and physiological media. Due to the generally poor bioavailability, new in vitro techniques were needed for screening of pharmacokinetic properties. An important parameter for these screening methods is the implementation at an early state of drug discovery phase, to find potential lead structures, before investment costs become significant. The established in vitro methods for the prediction of membrane interaction are not reliable especially for poorly soluble compounds. A new method that is fast and easy to use, requires only small amounts of NCE and which can provide more reliable predictions is needed. In this study, a new screening technique based on surface activity profiling for the prediction of oral drug absorption was evaluated with special emphasis on the predictability of biological membrane interaction of poorly soluble drug compounds. It was demonstrated that drug absorption through a bilayer membrane can be modeled by the orientation of compounds at the air/water interface. Thus amphilicity of a drug is generally related to both oral absorption and blood brain barrier penetration. In turn, amphiphilicity is influenced by the lipophilicity, size and charge distribution of a drug. Surface activity profiling was determined by analysis of surface pressure profiles using the Gibbs adsorption isotherm. The surface activity measurements were carried out using a multichannel tensiometer Delta 8, which was developed by Kibron to be utilized in conjugation high throughput screening in early drug discovery processes. For this study two test sets were analyzed, one for the prediction of gastrointestinal wall interaction and the second for the prediction of the penetration behavior at the blood brain barrier. Both test sets consist of drug compounds with a wide range of absorption properties and consist mainly of compounds with poor water solubility. Since the drugs characteristics varied, they were classified according to water solubility and surface activity and a sample preparation method for each group was established. For the prediction of oral drug absorption, three different methods were established to model the interaction of compound and gastrointestinal wall. For drug compounds with solubility above 1mmol/L the traditional shake-flask method enabled the determination of the amphiphilic properties of drug compounds in pure aqueous media. Compounds with solubility below 1mmol/L tend to not to exhibit any increase in surface activity. Thus surface tension measurements of compounds, which exhibited a limited surface activity due to poor aqueous solubility, were conducted from stock solutions prepared with various organic solvents. Mainly polar organic solvents were used. A mixture of DMSO and DMF resulted in the best combination of properties: the intensive solubility enhancing effect of DMF and the lower intrinsic surface activity of DMSO. The polar solvent ruptured the water clusters, so that highly lipophilic structures had a higher affinity to the solvent and higher concentrations could be obtained. For these compounds higher maximum surface pressure were generated than was possible in pure aqueous media. The surface pressure data were correlated with the fraction absorbed values in vivo However it was found that poor water solubility is not the only limiting step to exhibiting any surface activity. Some compounds were showed no surface activity in either solvent system. Therefore a micelle vehicle method was established using short chain phospholipids to mimic the gastrointestinal wall. It could be concluded from the results, that non surface active drugs can interact with the phospholipids micelle vehicle in a way analogous to their interaction with the membrane bilayer. The relative critical micelle concentration was correlated with the fraction absorbed of this test set. A sample preparation schema based on the three types of drugs was established. This schema enabled us to predict the absorbance of slightly soluble and poorly soluble drugs with acceptable reliability for early compound screening. For the prediction of blood brain barrier penetration using surface activity profiling as analyzing method, a test set with very poorly soluble characteristics was chosen. The sample preparation method was based on a strictly aqueous approach using the ‘shake flask’ method. The surface tension measurements enabled correlation of the amphiphilic properties of the very poorly soluble drug compounds with BBB uptake. From the aqueous surface pressure profiles and the determination of physicochemical parameters, it was found that blood brain barrier is more likely when a drug provides a small cross-sectional area, As, at the interface. The cross-sectional area is the only parameter which is independent from the maximal concentration in aqueous media and it is particularly suitable for lower solubility compounds. In summary, it was shown that amphilicity is related to biological membrane interaction in the human body and that surface activity profiling with appropriate sample preparation can be used as a reliable screening tool for the prediction of oral drug absorption of poorly soluble drugs. Furthermore an in vitro screening method of blood-brain-barrier penetration was established.$

جزئیات و درخواست

By Anna Christine Petereit
Publisher: Cuvillier Verlag, 2012-08-08
Pages: 202
Language: en
ISBN_13:9783736941649
ISBN_10:3736941641
Subject: Medical

Schedule of Classes

جزئیات و درخواست

By University of California, San Diego
1993
Pages: 136
Language: en
OTHER:UCSD:31822043025378
Subject: Schedules, School

Kleine Freuden

Roman | Ein hinreißender Roman über Pflichtgefühl und Begehr...

جزئیات و درخواست

By Clare Chambers
Publisher: Ullstein Buchverlage, 2021-08-30
Pages: 432
Language: de
ISBN_13:9783961611270
ISBN_10:3961611270
Subject: Fiction

By University of Cambridge
1991
Pages: 1546
Language: en
OTHER:UOM:39015076460693

Who's who in the East

جزئیات و درخواست

1943
Pages: 922
Language: en
OTHER:UOM:39015068970345
Subject: Biography

Portrait and Biographical Album of Warren County, Illinois

Containing Full Page Portraits and Biographical Sketches of ...

Free Epub

جزئیات و درخواست

1886
Pages: 816
Language: en
OTHER:UIUC:30112049814590
Subject: Warren County (Ill.)

Who's Who in the East, 1975-1976

جزئیات و درخواست

By Marquis Who's Who, LLC
1975-07
Pages: 828
Language: en
ISBN_10:0837906156
ISBN_13:9780837906157
Subject: Biography & Autobiography

Catalogue of the Columbian College in the District of Columbia

جزئیات و درخواست

By Columbian College in the District of Columbia
1938
Pages: 508
Language: en
OTHER:UOM:39015066579528

Catalogue of the Public Documents of the ... Congress and of All Departments of the Government of the United States for the Period from ... to ...

Free Epub

جزئیات و درخواست

By United States. Superintendent of Documents

Pages: 2868
Language: en
OTHER:IND:30000133148001
Subject: Government publications

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