Partition coefficient in octanol-water

Instead of using the oral bioavailability of a drug, one can attempt to correlate PM values with permeability coefficients generated from in situ perfused intestinal preparations. Here, one eliminates the complexities of liver metabolism, clearance, and formulation variables. Recently, this type of in vitro-in situ correlation has been conducted using the model peptides (described previously in Section V.B.2). The permeabilities of these model peptides were determined using a perfused rat intestinal preparation which involved cannulation of the mesenteric vein (Kim et al., 1993). With this preparation, it was possible to measure both the disappearance of the peptides from the intestinal perfusate and the appearance of the peptides in the mesenteric vein. Thus, clearance values (CLapp) could be calculated for each peptide. Knowing the effective surface area of the perfused rat ileum, the CLapp values could be converted to permeability coefficients (P). When the permeability coefficients of the model peptides were plotted as a function of the lipophilicity of the peptides, as measured by partition coefficients in octanol-water, a poor correlation (r2 = 0.02) was observed. A better correlation was observed between the permeabilities of these peptides and the number of potential hydrogen bonds the peptide can make with water (r2 = 0.56,... 

A log P Difference between log P in octanol/water and alkane/water log D Logarithm of the distribution coefficient in octanol/water at pH 7.4 log P Logarithm of the partition coefficient in octanol/water (for neutral species)... 

Fig. 7. Estimates of the logarithm of partition coefficient in octanol water (log P) of 4-PIOL analog substituents obtained by use of Crippen s fragmentation method. Correlation between affinity tpAT,) and lipophilicity (log P) of the substituents of the 4-PIOL analogs. The two gray lines connect the high-affinity compounds (open squares) and the low-affinity compounds (open triangles), respectively, and the black line shows the correlation between the remaining compounds (black circles).

The retention times of test solutes are correlated with reference compounds whose partition coefficients in octanol/water (Kow) are known The reliability of this technique depends on the extent to which the stationary and mobile phases simulate the octanol/water system... 

The partition coefficient in octanol/water of clopidogrel bisulfate has been reported to be about 3.9 at pH 7.4 [3]. 

British Pharmacopoeia 2009 and European Pharmacopoeia 6.0 [3,7] specify fhat glimepiride is insoluble in water but it is soluble in dimethylforma-mide, slightly soluble in methylene chloride and very slightly soluble in methanol. Further, its log partition coefficient in octanol-water is 3.81, with log distribution coefficient in octanol-phosphate buffer pH 7.4 valued for 2.38 [8]. The value of glimepiride was found fo be 6.2 0.1 at 37 °C [2]. 

Thus, Collander s equation 42, which was established from empirical studies (111), is theoretically derived from the extrathermo-dynamic treatment of solvent effects and is obtained as a result of the second approximation which takes into account the effects of solvation on the interaction term between R and x> x S we now regard the interaction of drugs (in water) with tfie bio-phase as a partitioning phenomenon, equation 42 becomes the basis for the use of the partition coefficient in octanol/water, P, as a model for the partition coefficient between biophase and water,... 

The pKa values of some antiinflammatory arylaliphatic acids, including alclofenac and ibuprofen, were measured potentiometrically in dimethyl sulfoxide/water. The values were confirmed by assessing the solubility of the acids as a function of the pH of the aqueous solutions. In this way, the intrinsic partition coefficient in octanol/ water was defined."... 

Figure 20 Correlation of appearance kinetics of steroid permeants across Caco-2 cell monolayers in the Trans well system with log partition coefficients (n-octanol/water) and stirring dependency. 

Passive diffusion through the lipid bilayer of the epithelium can be described using the partition coefficient between octanol/water (log P) and A log P (the difference between the partition into octanol/water and heptane/ethylene glycol or heptane/ octanol) [157, 158], The lipophilicity of the drug (log P) (or rather log D at a certain pH) can easily be either measured or calculated, and is therefore generally used as a predictor of drug permeability. Recently, a method using artificial membrane permeation (PAMPA) has also been found to describe the passive diffusion in a similar manner to the Caco-2 cell monolayers [159]. 

The assessment of rate and distribution of environmental pollutants in various phases including air, water, and soil is important for the risk assessment of chemicals [48]. The partitioning of chemicals among different phases is usually assessed using a critical list of physical properties including vapor pressure (VP), aqueous solubility, ainwater partition coefficient, and octanol-water partition coefficient. 

Chapters 4, 5, and 6 discuss estimation methods for these partition coefficients. The octanol-water partition coefficient KqW is frequently designated P in the medicinal and biological chemistry literature. 

However, when using the ACD program for calculating partition coefficients, a octanol water logP value of 3.59 0.41 was calculated. Using the ACD program that calculated the pH distribution of distribution coefficients, the data plotted in Figure 2 were obtained. 

For a number of solutes, the partition coefficients in octanol could be well reproduced by Eq. 6.11 (Figure 6.5), as could the differences in the partitioning between octanol-water and hydrocarbon-water systems. A relatively large difference of 1.7 kcal/mol between experimental and calculated values was observed only for glycerol,... 

In a solute-solvent system of similar polarity (naphthalene in chlorobenzene), Equation (3.34) can estimate the solubility of the liquid solute. If the polarities of the solute and the solvent are very different (naphthalene in n-hexane), Equation (3.34) should be modified. The partition coefficient in the water-octanol system can be used for differences in polarities of the solute and the solvent. The partition coefficient of a liquid solute, Kw0, in the water-octanol system is defined as ... 

Since the mole fraction-based partition coefficient of a dilute species between two liquid phases is the inverse of the ratio of its infinite dilution activity coefficients in each phase, the GCS model can also be used for such predictions. Among the many possible partition coefficients, the octanol-water partition coefficient, Aqw, is of special interest. For example, A/ow is a key parameter in determining the fate of a persistent organic pollutant... 

FIGURE 6 Phase distribution equilibria involving pure phases with importance for describing environmental phase partitioning. Kaw, air-water partition coefficient Kow, octanol-water partition coefficient Kqa, octanol-air partition coefficient Pl, (supercooled) liquid vapor pressure Cw and Co, saturation solubility in water and octanol, respectively yw and yo, activity coefficient in water and octanol, respectively. 

The activity of the preservative depends on the concentration in the aqueous phase and therefore on the partition coefficient (n-octanol/water). Because of its relatively favourable partition coefficient sorbic acid is a suitable preservative for o/w emulsions. Therefore it is often used in hydrophilic cream bases. Sorbic acid holds a carboxyl group that is deprotonated above pH 4—5. Sorbic acid only takes effect in the non-ionised form that means only in acidic solutions. However, at relatively low pH sorbic acid is degraded by oxidation. To prevent oxidation sorbic acid is often used in combination with potassium sorbate in order to obtain a pH value of 4-5. 

C in equation (2) is a molar concentration which produces a certain biological effect, P is the -octanol/water partition coefficient (see Octanol/Water Partition Coefficients), and a is the electronic Hammett constant (equation 1). The definition of a parabolic model and the combination of different physicochemical properties in one model allowed for the first time the description of structure-activity relationships which could not be correlated with a single linear term. As an alternative to log P values, a lipophilicity parameter n can be used which is defined in an analogous manner as the electronic a parameter (1 equation 3). " ... 

Octanol—Water Partition Coefficient. In environmental calculations, the octanol—water partition coefficient, is related to a chemical s Hpophilicity and... 

By modeling the substance behavior at the interface of two liquid phases, in particular, stationary and mobile phases in liquid chromatography, 1-octanol - water partition coefficients or partition coefficients in... 

Aqueous solutions are not suitable solvents for esterifications and transesterifications, and these reactions are carried out in organic solvents of low polarity [9-12]. However, enzymes are surrounded by a hydration shell or bound water that is required for the retention of structure and catalytic activity [13]. Polar hydrophilic solvents such as DMF, DMSO, acetone, and alcohols (log P<0, where P is the partition coefficient between octanol and water) are incompatible and lead to rapid denaturation. Common solvents for esterifications and transesterifications include alkanes (hexane/log P=3.5), aromatics (toluene/2.5, benzene/2), haloalkanes (CHCI3/2, CH2CI2/I.4), and ethers (diisopropyl ether/1.9, terf-butylmethyl ether/ 0.94, diethyl ether/0.85). Exceptionally stable enzymes such as Candida antarctica lipase B (CAL-B) have been used in more polar solvents (tetrahydrofuran/0.49, acetonitrile/—0.33). Room-temperature ionic liquids [14—17] and supercritical fluids [18] are also good media for a wide range of biotransformations. 

The BUSES model provides an estimate of the organic carbon/water partition coefficient (Koc) based on the octanol/water partition coefficient (Kow)- From these data, it is evident that the methyltins are less likely to partition onto organic carbon (in sediments, soils, biota) than are the butyl- and octyltin compormds due to then-lower partition coefficients and higher water solubilities. The 7/oc value can then be used to derive sohds/water partition coefficients in suspended matter, in sediment, and in soil using values of 10%, 5%, and 2% for organie carbon, representing typical organic carbon contents of suspended matter, sediment, and soil, respeetively. 

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