Partition, distribution coefficient

We return to using the Kp and Kd symbols to represent the partition coefficient and the apparent partition (distribution) coefficient, respectively. The effective, apparent, membrane, and intrinsic permeability coefficients are denoted Pe, Pa, Pm, and P0, respectively, and D refers to the diffusivity of molecules. 

The partition coefficient is needed to determine the moles lost to the membrane, VM CM(t). If ionizable compounds are considered, then one must decide on the types of partition coefficient to use -Kp (true pH-independent partition coefficient) or Kd (pH-dependent apparent partition coefficient). If the permeability assay is based on the measurement of the total concentrations, Cn(t) and CA(t), summed over all charge-state forms of the molecule, and only the uncharged molecules transport across the membrane to an appreciable extent, it is necessary to consider the apparent partition (distribution) coefficient, Kd, in order to explain the pH dependence of permeability. 

The apparent membrane-buffer partition (distribution) coefficient Kd, defined at... 

Partition (distribution) coefficients, P (D) - often reported as logio P or logio D, have been measured for a large number of... 

Partition (Distribution) Coefficients In describing the partitioning of a trace element among coexisting phases, we frequently use a partition (distribution) coefficient for a given element, defined as a concentration ratio C2/Cj. Here C is concentration, and the subscripts identify the phases often the normalizing phase is some convenient reservoir, such as a silicate melt, with which several other phases may equilibrate. For noble gases, it is often most convenient to normalize to a gas phase. If the concentrations are expressed in the same units, the distribution coefficient is dimensionless. It is conventional to cite noble gas concentrations in condensed phases in cm3 STP/g, however, and to describe the gas phase by partial... 

Description of key chemical and physical properties/ characteristics—A physical description of the compound (color, form, and appearance) should be stated. A discussion should be provided on existence of pol3miorphic forms, solvates or hydrates of the molecule supported by appropriate data (e.g., thermal analyses or x-ray powder diffraction testing). Available solubility data, specific (optical) rotation values for chiral compounds, the partition (distribution) coefficient, acid/base dissociation constants, pH, and hygroscopi-city data are generally also included for the selected form of the API. 

Partition/distribution coefficients (logP and D) RP-HPLC logit Shake-flask/HPLC Dual-phase potentiometric titration Octanol coated colunms Liquid artificial membranes... 

The most Important experimental fact to support this conclusion was given by the static (equilibrium) partitioning experiments (ref. 11 14), which confirmed the agreement of partition (distribution) coefficients, K q s, determined from both static and chromatographic measurements. Fig. 1 shows an example of such results. 

The chromatographic partition (distribution) coefficient for dissolution, K, given by eqn (2.38) will be denoted by K, in this section to distinguish it from partition coefficients for adsorption at the gas-liquid, and gas-solid, Ka, interfaces. It is defined by the ratio of solute molar concentration in stationary and mobile phase ... 

The constant K is termed the distribution or partition coefficient. As a very rough approximation the distribution coefficient may be assumed equal to the ratio of the solubilities in the two solvents. Organic compounds are usually relatively more soluble in organic solvents than in water, hence they may be extracted from aqueous solutions. If electrolytes, e.g., sodium chloride, are added to the aqueous solution, the solubility of the organic substance is lowered, i.e., it will be salted out this will assist the extraction of the organic compound. 

The principle of headspace sampling is introduced in this experiment using a mixture of methanol, chloroform, 1,2-dichloroethane, 1,1,1-trichloroethane, benzene, toluene, and p-xylene. Directions are given for evaluating the distribution coefficient for the partitioning of a volatile species between the liquid and vapor phase and for its quantitative analysis in the liquid phase. Both packed (OV-101) and capillary (5% phenyl silicone) columns were used. The GG is equipped with a flame ionization detector. 

Distribution Coefficients. Gel-permeation stationary-phase chromatography normally exhibits symmetrical (Gaussian) peaks because the partitioning of the solute between mobile and stationary phases is linear. Criteria more sophisticated than those represented in Figure 8 are seldom used (34). 

S. W. Karickhoff and D. S. Brown, determination of Octanol Water Distribution Coefficients, Water Solubilities, and Sediment/Water Partitions Coefficientsfor Hydrophobic Organic Pollutants, EPA-600/4-79-032, report, EPA, Washington, D.C., 1979. 

Extraction from Aqueous Solutions Critical Fluid Technologies, Inc. has developed a continuous countercurrent extraction process based on a 0.5-oy 10-m column to extract residual organic solvents such as trichloroethylene, methylene chloride, benzene, and chloroform from industrial wastewater streams. Typical solvents include supercritical CO9 and near-critical propane. The economics of these processes are largely driven by the hydrophihcity of the product, which has a large influence on the distribution coefficient. For example, at 16°C, the partition coefficient between liquid CO9 and water is 0.4 for methanol, 1.8 for /i-butanol, and 31 for /i-heptanol. 

Apparent partition coefficient (logZ)) at an ionic strength of / = 0.02M, log P value of the neutral microspecies and the acidic dissociation constant of 5 was calculated (97ANC4143). The distribution coefficient of 5 was determined between 1-octanol and universal buffer in the pH range 3-10 at a... 

Teilunga-brucb, m. Math.) partial fraction, -ebene, /. plane of division, -flacbe, /. (Geol.) division plane, -gesetz, n. law of partition, -koeffizient, m. partition coefficient, distribution coefficient, -zabl, /. dividend. -zeicben, n. mark of division hyphen, -zustand, m. state of division. Teil-verflUssigung,/. partial liquefaction, -vor-gang, m. partial process, -wand, /. division wall. 

Lipophilicity represents the affinity of a molecule or a moiety for a lipophilic (= fat-loving) environment and is commonly measured by the partition coefficient, (where aaa represent a generic biphasic system, e.g. oct indicates the standard octanol-water). P is valid for a single electrical species, to be specified (P for neutral forms and P for ionized species). The distribution coefficient, expressed as is a pH-dependent descriptor (Eq. 3) for ionizable solutes and results from the weighted contributions of all electrical forms present at this pH ... 

A general definition of log P and log D, in its simplest form, can be given as the logarithm of the ratio (P or D) of the concentration of species of interest (the drug in a pharmaceutical context) in each phase, assuming the phases are immiscible and well separated prior to analysis. P is defined as the partition coefficient, whereas D is the distribution coefficient. However, the simplest form does not reveal some of the intricacies of the determination and use of these parameters, and further explanation is necessary. 

While there are plenty of methods to predict 1-octanol-water partition coefficients, logP (see Chapters 14 and 15), the number of approaches to predict 1-octanol-water distribution coefficients is rather limited. This is due to a lower availability of log D data and, in general, higher computational complexity of this property compared to that of log P. The approaches to predict log D can be roughly classified into two major categories (i) calculation of log D at an arbitrary pH and (ii) calculation of log D at a fixed pH. 

These are more general, and they can perform log D calculation at any pH and ionic strength. The distribution coefficient for monoprotic base given by Eq. (2) can be simplified to Eq. (3) assuming that only the neutral form of a molecule will partition into the organic phase and thus D is zero. 

On the other hand, the ratio of total concentrations of ionized and nonionized species between both phases is named distribution coefficient (symbolized as D). It is often referred to as an effective or apparent partition coefficient and, in concentration terms, it is mathematically defined as ... 

Of course, the shape of the lipophilicity profiles becomes much more complicated for molecules with multiple ionized forms. Nevertheless, the partition coefficients may be calculated from the distribution coefficient using the general equation [113] ... 

Hence, two drugs of similar ogP may differ greatly in logZ) at physiological pH, with profound consequences for their pharmacological activity. As a consequence, log/ values of ionizable compounds are often quoted at pH 7.4, and equations similar to those above are used in pH-metric techniques [117-124] to determine either log/ or logZ). A compilation of the principal relationships linking partition and distribution coefficients is available in Refs. 125 and 126. 

However, recent studies on the variation of the distribution coefficient of ionizable drugs as a function of pH (pH-lipophilicity profiles) shows that the partitioning of charged species cannot be neglected [143]. In other words, the general relationship between distribution and partition coefficients [Eq. (15)] cannot be simplified. 

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