Ionic Drugs

DRUG RELEASE FROM IONIC DRUGS FROM WATER-INSOLUBLE DRUG-POLYION COMPLEX TABLETS... 

Drug Release from Ionic Drugs from Water-Insoluble Drug-Polyion Complex Tablets... 

Design principles of new sensors for ionic drugs follow from application of potential gjnerjtion theory using three ions M, X and Y, or M, N and Y. Studies of liquid/liquid interface transport identify single-ion free energies of partition as the figures of merit for selectivity and sensitivity. New liquid membranes with sensitivities to 10 mol/1 for bisquaternary muscle relaxants and phenytoin serve as examples. 

Masada, T., et al. 1989. Examination of iontophoretic transport of ionic drugs across skin Baseline studies with the four-electrode system. Int J Pharm 49 57. 

Rizk, N. I., and Stevens, C. L. Implantable electrophoretic pump for ionic drugs and associated methods, U.S. Patent 4639244, 1987. 

W. Steuer, J. Baumann, and F. Erni, Separation of ionic drug substances by supercritical fluid chromatography, J. Chromatogr., 500 469(1990). 

The effect of different polymer bases and additives on percutaneous absorption of these two ionic drugs are examined. Carboxyvinylpolymer (CVP), an ionic polymer film base, yields films with poor bioavailability of cationic drugs such as DIL, but is effective for films containing anionic drugs such as DSCG. In contrast, polyvinyl alcohol (PVA) and glycerol, electrically neutral bases, were used to formulate films with good bioavailability. 

Another important factor is the influence of drug ionization on the partition coefficient and this is particularly important when a buffer is used instead of water. The partition coefficient determined from Equation (14) is an apparent value rather than a true partition coefficient for ionic drugs. However, the true partition coefficient can be calculated from the apparent partition coefficient if the drug s pA a and the pH of the drug solution are known [39], as shown in the equations... 

For ionic drugs the salt form can be considered as an alternative to increase the solubility. Drug substance usually is more soluble in aqueous media in its ionic form. Low solubility of the neutral form of the drug substance suggests the necessity to formulate it in the form of salt. The reader is referred to reference 46 for more information about the properties, selection, and use of salt forms for future drug development. Examples of commonly used salt counterions are shown in Table 12-6. 

Unlike enantiomers, diastereomers have different solubilities in an achiral environment. Many chiral counterions, such as arginine and lysine, are commonly used to prepare salts of an ionic drug in order to improve its pharmaceutically relevant properties. However, when the drug is chiral, a chiral counterion should be used with caution. If the drug or the counterion is racemic, diastereomeric salts will be formed, constituting a heterogeneous system. Because the solubilities of diastereomers differ, a diastereomeric mixture of chiral salts is undesirable in a formulation. 

A useful method for dealing with a highly polar ionic drug is to convert it into a neutral ion-pair (IP) complex by the addition of an excess of suitable ions of opposite charge, followed by extraction of the complex into an organic solvent. 

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