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Evolutionary genomics of inversions in Drosophila pseudoobscura: Evidence for epistasis
- S. Schaeffer, M. P. Goetting-Minesky, W. Anderson
- BiologyProceedings of the National Academy of Sciences…
- 24 June 2003
The hypothesis that the inversions of D. pseudoobscura have emerged as suppressors of recombination to maintain positive epistatic relationships among loci within gene arrangements that developed as the species adapted to a heterogeneous environment is supported.
Prediction of Solubility and Permeability Class Membership: Provisional BCS Classification of the World’s Top Oral Drugs
One notable finding of the provisional BCS classification is that the clinical performance of the majority of approved IR oral drug products essential for human health can be assured with an in vitro dissolution test, rather than empirical in vivo human studies.
Impaired Arteriogenic Response to Acute Hindlimb Ischemia in CD4-Knockout Mice
The data suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenesis cytokines.
The solubility-permeability interplay in using cyclodextrins as pharmaceutical solubilizers: mechanistic modeling and application to progesterone.
- A. Dahan, Jonathan M. Miller, A. Hoffman, G. Amidon, G. Amidon
- BiologyJournal of pharmaceutical sciences
- 1 June 2010
This work demonstrates that when using cyclodextrins as pharmaceutical solubilizers, a trade-off exists between solubility increase and permeability decrease that must not be overlooked; the transport model presented here can aid in striking the appropriatesolubility-permeability balance in order to achieve optimal overall absorption.
Identifying the Stable Polymorph Early in the Drug Discovery–Development Process
- Jonathan M. Miller, Benjamin M. Collman, Landon R Greene, D. Grant, A. Blackburn
- Materials Science, BiologyPharmaceutical development and technology
- 1 January 2005
A screen for discovering the stable polymorph of a pharmaceutical compound early in the drug discovery–development process is developed and described and Ritonavir and an early development candidate are used as model compounds to demonstrate the utility of the screen.
Quasi-equilibrium analysis of the ion-pair mediated membrane transport of low-permeability drugs.
The Solubility–Permeability Interplay and Its Implications in Formulation Design and Development for Poorly Soluble Drugs
It has been shown that decreased apparent permeability accompanies the solubility increase when using different solubilization methods, and the weight of the evidence indicates that thesolubility–permeability interplay cannot be ignored when using solubilty-enabling formulations.
The solubility-permeability interplay when using cosolvents for solubilization: revising the way we use solubility-enabling formulations.
- Jonathan M. Miller, Avital Beig, R. Carr, G. Webster, A. Dahan
- ChemistryMolecular pharmaceutics
- 22 February 2012
This work demonstrates that a direct trade-off exists between the apparentsolubility and permeability, which must be taken into account when developing solubility-enabling formulations to strike the optimal solubilty-permeability balance, in order to maximize the overall oral absorption.
Semi‐empirical relationships between effective mobility, charge, and molecular weight of pharmaceuticals by pressure‐assisted capillary electrophoresis: Applications in drug discovery
- Jonathan M. Miller, A. Blackburn, Yi Shi, Andrew J. Melzak, Howard Y. Ando
- 1 September 2002
The meff, Zc/MWx relationships were applied to developing a technique for selecting an appropriate pH to achieve optimal separation of pharmaceuticals and determining the maximum charge of a molecule in the pH range of determination of negative log of the dissociation constants by PACE, thus enabling the correct choice of model equation to be automated without structure analysis.
Striking the Optimal Solubility-Permeability Balance in Oral Formulation Development for Lipophilic Drugs: Maximizing Carbamazepine Blood Levels.
This work demonstrates the in vivo solubility-permeability trade-off in oral delivery of lipophilic drugs; when a solubilities-enabling formulation is developed, minimal threshold solubilty should be targeted, that is just enough to allow solubilization of the drug dose throughout the GIT, while excess solubILizer should be avoided.