Partition coefficients liposome-water

The use of partition coefficients between water and lipophilic media is of wide use in pharmaceutical research. As discussed in the last chapters, different lipophilicity scales are used to describe the lipophilicity of a compound and relate it to its absorption behaviour in vivo. Differences between the logPow and partitioning between phospholipids and water (mainly determined using liposomes) for diverse compounds have been described leading to the development of the immobilized artificial membrane chromatography system. However, also the predictivity of the IAM system is limited and only a small number of membrane systems are available. 

Octanol" and "Membrane" pK in Partition Coefficients Measurement 67 Tab. 3.1 Octanol-water and liposome-water partition coefficients. ... 

Avdeef, A., Box, K. J., Comer, J. E., Hibbert, C., Tam, K. Y. pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs. Pharm. Res. 1998,... 

A method where phospholipids are entrapped in the pores of resin beads, in the forms of multilamellar vesicles, has been described [313-319,376]. In some ways, the idea is similar to that of IAM chromatography, even though the resin is modified differently. The retention indices correlate very well with the partition coefficients measured in liposome-water systems (described below). 

Figure 5.3 The effect of hydrogen bonding and steric hindrance on the difference between liposome-water and octanol-water partition coefficients 8 increased H-bond donor strength and decreased steric hindrance favor membrane partitioning in the substituted phenols [381]. [Avdeef, A., Cun Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

TABLE 5.3 Critically Selected Experimental Liposome-Water Partition Coefficients... 

TABLE 5.4 Liposome-Water Partition Coefficients of Substituted Phenols and Other Compounds... 

Bums, S. T. Khaledi, M. G., Rapid determination of liposome-water partition coefficient (Kiw) using liposome electrokinetic chromatography (LEKC), J. Pharm. Sci. 91, 1601— 1612 (2002). 

Principal differences between bulk media water and membrane water partition coefficients are listed in Table 2. These differences are essentially based on the several orders of magnitude difference in surface-to-volume ratio. In the liposomal system, charges built up due to sorption of charged species can be electrically neutralised by counter-ions from the electrolyte (diffuse double... 

Estimation is easier and less time-consuming because use is made of empirical relationships between the BCF and physicochemical properties of the compound, such as water solubility (S) [42-48], Km, (solid organic carbon/water partition coefficient) [48], Kmw (membrane water partition coefficient), iipw (liposome water partition coefficient) [49], critical micelle concentration (CMC) [45], steric factors, molecular weight [47,48], and others. The most common regression method is the estimation of BCF from the octanol-water partition coefficient (Kovl) [18,42,44-48,50,51],... 

Takagi, T., Kimura, A., Da, Y. Z., Nakai, H., and Fujiwara, H. Partition coefficients in a liposome/water system. Methods for determination and error analysis, Anal Scl, 8(6) 761-765, 1992. 

A Avdeef, KJ Box, JEA Comer, C Hibbert, KY Tam. pH-Metric log P 10. Determination of liposomal membrane-water partition coefficients of ioniz-able drugs. Pharm Res 15 209-215, 1998. 

Table 10.2 Organic Phase-Water Partition Coefficients of Some Organic Compounds for Various Organic Phases Octanol (o), Triacylglycerides (tag), Liposomes (lips), Proteins (prot), Cutin (cut), and Lignin (lig). (All values except Kiow in L kg"1 org. phase for 20-25°C if not otherwise stated. Note that the densities of the organic phases are close to 1 kg org. phase L 1 org. phase.)...

Figure 10.13 Plot of log 1/LC,S0 for guppies (small tropical fish, Poecilia reticulata) versus (a) log octanol-water partition constant (log A ,ow), and (b) log L-a-dimyristoylphosphatidylcholine liposome-water coefficient (log A)]ipsw) for a series of neutral apolar and weakly polar (o) and polar (t) compounds. Data from Gobas et al. (1988), Vaes et al. (1998), and Gunatilleka and Poole (1999).

Tab. 2.7 Partition coefficient, log P, log D, and related parameters of compounds 1—7 in the liposome-water system.3 (Adapted from Table 2 of ref. 48)...

Fig. 2.3 Relative lipophilicities of compounds 1—7. (A) Relation between the partition coefficients of the neutral and cationic forms (log and log / respectively) in octanol—water. (B) Relation between the partition coefficients of the neutral and cationic forms in the liposome-water system. (C) Bilinear relation between log D7 5 in octanol-water and liposome-water. (Reprinted from Fig. 2 of ref. 48 with permission from Kluwer Academic/Plenum Publishers.)...

DSC has also been used to determine partition coefficients between phospholipids and water, avoiding radiolabeled solutes and high concentrations. One example is the partitioning of cardiac drugs into DMPC liposomes [48] (Table 3.9). The drug concentration in the liposomes was calculated using the following equation ... 

Tab. 4.34 Partition coefficients of Ca2+ antagonists in synaptic plasma membranes (SPM) and liposomes and octanol-water, at 25 °C. (Reprinted from Tab. 1 of ref. 122 with permission from Elsevier Science)...

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