Hydrophobic drugs variety

This technique, based on the precipitation of a hydrophobic polymer, is useful for the encapsulation of either hydrophilic or hydrophobic drugs because a variety of solvents, including polar (e.g., acetone or methanol) and non-polar (methylene chloride or chloroform) solvents can be chosen for dissolving the drug. This procedure is just like nanoprecipitation, however, the miscibility of both phases is prevented by the saturation of the external aqueous phase with PVA. Precipitation occurs when a sufficient amount of water is added to allow complete diffusion of the acetone into the aqueous phase. 

For a variety of other peptides and also for more hydrophobic drugs, negative enthalpies for binding or incorporation have been observed. For these molecules, as discussed above for the incorporation of filipin into bilayers, the observed heat effects contain contributions from other than purely hydrophobic effects. Therefore, the only thennodynamic function containing reliable infonnation on changes of hydrophobic hydration is Ac/7. However, in many cases, the temperature dependence of the heat of reaction has not been detennined. 

The work by Hammett and Taft in the 1950s had been dedicated to the separation and quantification of steric and electronic influences on chemical reactivity. Building on this, from 1964 onwards Hansch started to quantify the steric, electrostatic, and hydrophobic effects and their influences on a variety of properties, not least on the biological activity of drugs. In 1964, the Free-Wilson analysis was introduced to relate biological activity to the presence or absence of certain substructures in a molecule. 

Molecules with a large molecular weight or size are confined to the transcellular route and its requirements related to the hydrophobicity of the molecule. The transcellular pathway has been evaluated for many years and is thought to be the main route of absorption of many drugs, both with respect to carrier-mediated transport and passive diffusion. The most well-known requirement for the passive part of this route is hydrophobicity, and a relationship between permeability coefficients across cell monolayers such as the Caco-2 versus log P and log D 7.4 or 6.5 have been established [102, 117]. However, this relationship appears to be nonlinear and reaches a plateau at around log P of 2, while higher lipophilicities result in reduced permeability [102, 117, 118]. Because of this, much more attention has recently been paid towards molecular descriptors other than lipophilicity [86, 119-125] (see section 5.5.6.). The relative contribution between the para-cellular and transcellular components has also been evaluated using Caco-2 cells, and for a variety of compounds with different charges [110, 112] and sizes [112] (see Section 5.4.5). 

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