Charged drugs

Fischer, H., Kansy, M., Bur, D. CAFCA a novel tool for the calculation of amphiphilic properties of charged drug molecules. Chimia 2000, 54, 640-645. 

Such ion-pair constants are conditional , in that they depend on the concentration of the counterion with which the charged drug molecule enters into the octanol phase as an ion-pair. This is due to the low dielectric property of octanol, inducing charge neutrality upon uptake of charged drug molecules. Extraction constants may be used to explicitly include the participahon of the counterion [18]. 

For multi-pH liposome-water distribution measurements in 0.15 M NaCl or KCl solutions, the difference between the true pKj and pK (and between logPMBM and logPMBM) is about 1 log unit for bases and 2 log units for acids. Liposomes formed from phosphatidylcholine have a tendency to stabilize the charged drug more effectively than that in the octanol-water system [71]. Table 3.1 shows liposome-water examples of the relative pKj shifts. The average values cited in the examples are close the diff 1-2 approximation noted above. 

Lee, A. G., Effects of charged drugs on the phase transition temperature of phospholipid bilayers, Biochim. Biophys. Acta 514, 95-104 (1978). 

The microscopic rate constants for association and dissociation at a site within an electric field (for block by charged drugs) are exponential functions of the membrane voltage ... 

Figure 20 Ion exchange of positively charged drug bound to negatively charged polymer network with hydronium ion generated by electrolysis of water by electric current.

Cross-resistance to [Ru(r 6-bip)Cl(en)]PF6 in A2780ad fell from a factor of 38 to only threefold upon co-administration of verapamil, indicating that P-glycoprotein mediated active efflux of the anticancer drug was predominantly responsible for the observed cross-resistance and could be abrogated by addition of the competitive inhibitor. Such behavior is common for lipophilic positively charged drugs. 

Electrostatic forces are due to the ionic charges residing on the molecules, which attract or repel each other. The macromolecular structures of the receptors and enzymes mean that there are a number of ionic charges to attract the oppositely charged drug molecules. The forces of electrostatic interactions are weaker than covalent bonding. Electrostatic interactions are more common in drug-receptor interactions. There are two types of electrostatic interactions ... 

In this study, we report the release properties of two new polyelectrolyte materials poly(acrylamido-methyl-propanesulfonate) (PAMPS) and poly (diallydimethyl ammonium chloride) (PDADMAC), which were used as anionic and cationic carriers, respectively, for oppositely charged drugs. These polymers proved to be very promising and practical as erodible carriers for controlled drug delivery as they are available commerically. Binding ionic moieties to the linear polymer backbone can be done by a simple mixing process. 

Fig. 5 Relationship between the log Ks values obtained by chromatography on entrapped egg yolk phospholipid (EPL) liposomes and the log Poct values from oc-tanol/water partitioning analyses, for neutral drugs (upper line) and for positively (center line) and negatively (lower line) charged drugs. (Reprinted with permission from Ref. 27. Copyright 2001 Elsevier Science.)...

The ACE analysis of interactions between drugs and phospholipid bilayers of liposomes present as a pseudostationary phase was performed by Zhang et al. (32). The capillaries were treated to eliminate electroendosmosis. Freshly prepared and essentially neutral small unilamellar liposomes composed of egg phosphatidylcholine were sucked into the capillary. These liposomes increased both the retention of four negatively charged drugs and the separation between the substances (Fig. 6). The chromatographic retentions of these drugs on immobilized phosphatidylcholine liposomes, ex-... 

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