Ion-Exchange Resins as Drug Delivery Carriers

Resins used are polymers that contain appropriatelysubstituted acidic groups, such as carboxylic and sulfonic for cation exchangers; or basic groups, such as quaternary ammonium group for anion exchangers.

Ion exchange resins have been widely studied and marketed. Salts of cationic and anionic exchange resins are insoluble complexes in which drug release results from exchange of bound drug ions by ions normally present in body fluids from both acidic and basic drugs.

Strongly acidic cation exchange resin

Sulphonated polystyrene

=strongly acidic cation exchange resin (SAC)

SO3H SO3H SO3H SO3H

Sulphonic group

Amberjet 1200 H, Amberlite IR120 HAmberjet 1200 H, Amberlite IR120 H

Weakly acidic cation exchange resin (WAC)

CH2

CH CH CH

COOH COOH COOH

CH2 CH2

Polycarboxylic acid, polyacrylic acid

Amberlite IRC86Amberlite IRC86

Quaternary ammonium

Strongly basic anion exchange resin (SBA)

CH3

+Cl

-

NCH2 CH3

CH3

Amberlite IRA 402 Cl, Amberjet 4200 ClAmberlite IRA 402 Cl, Amberjet 4200 Cl

CH2 NCH3

CH3

Weakly basic anion exchange resin (WBA)

POLYSTYRENE, QUATERNARY AMMONIUM, CHLORIDE

POLYSTYRENE, TRIMRTHYLAMINE

Preparation

The resin is allowed to swell for a definite period of time inwater. Accurately weighed amount of (drug: resin ratio) isadded and stirred for desired period of time. The mixture isfiltered and residue is washed with deionized water. Filtrateis analyzed analyzed by U.V. or HPLC for the unbounddrug and percentage drug loading or degree ofencapsulation is calculated as (Total drug added-free drugin the filtrate)/ Total drug added). Factors that affect drugloading: Degree of cross-linking, mixing time, pH,temperature, resin particles size and drug:resin ratio. Theresin beads can be coated with sustained release polymerto sustain the drug release

Factors Affecting Resin Performance

1 .Degree of cross linking Extent of cross linkage has tremendous effect on drug loading efficiency. If resin is having less degree of cross linking, then it is more porous and the extent of swelling due to hydration is more. Whereas, if it is less cross linked, then it has less swelling. Because of this, the drug loading ability of less cross linked resin is high than more cross linked. But, the drug release from former is rapid and sustained from latter ones .

2 .Particle sizeThe smaller resin beads offering more surface area have shown rapid exchange of ions with shorter diffusion path length. Whereas, the larger beads, have more diffusional path length leading to sustained release.

3 .Mixing timeWith increase in the mixing time, the swelling of resin goes on increasing and ultimately drug loading. In the initial phases, the drug loading seen

is more and later on it is less .

4. pH

pH is an important factor affecting drug complexation efficiency

and drug release from drug resin complex. If the pH of

surrounding medium is acidic then it promotes dissociation of

basic drugs leading to formation of more ionic species available

for drug loading. Towards alkaline pH, the dissociation of acidic

drugs will be promoted. With increase in dissociation the

complexation efficiency gets improved.

5 .temperature

For certain resins the effect of temperature on drug loading has been reported. High temperature may also cause swelling of resin. Cation exchange resin doesn’t get significantly affected

by temperature changes unlike anion exchangers .

Exchange mechanism

Anionic drugs:

CI- + resin- {N(CH3 )3+Drug (-)

resin- {N(CH3 )3+CI- + Drug-

Positively charged Negatively

charged

H+ + resin- SO3 - Drug +

resin- SO3 - H+ + Drug +

Anionic drugs

Positively charged

Negatively charged

1. Oral modified release formulations:

Several preparations involving strong resinates of sulfuric acid (cation exchange resins) provided more moderate release than the weak resinates of carboxylic acid. Hence, resinates of strong cationic drugs are formulated as sustained release suspension, tablets, capsules and microparticles. Oral modified release formulations. Polymeric coating using ethyl cellulose and been reported for exercising control over drug release.

2. Fast disintegrating tablets:

Resins although insoluble, have great affinity for water and hence, act as disintegrant. Moreover, when have small particle size the rate of swelling is high making them superdisintegrant.

Drug Delivery Applications

3 .Improved DissolutionDrug resin complexation converts drug to amorphous form. Hence , drugs with poor solubility, during the process of desorption, immediately releases the drug leading to improved drug dissolution.

4. Taste MaskingThe taste perception of bitter drugs is experienced in the mouth at taste buds. When complexed drug resinates doesn’t release drug in mouth because of shortage of exchangeable ions in the saliva, taste can be masked.