ION EXCHANGE RESINS:

Ion exchange resins are solid and suitably insolubilized high molecular weight
polyelectrolyte’s which can exchange mobile ions of similar charges with the surrounding
medium reversibly and stochiometrically.

An ion exchange resins exhibited like small bead with a diameter between 1-2 mm, it is
fabricated from an organic polymer substrate backbone.

They are available in desired size ranges.

Advantages[5]of ion exchange resins include

Economic and readily available

.Free from local and systemic toxicities.

Drug-resinates can be formulated into various dosage forms like tablets, capsules,
suspensions etc.

Can be used for several purposes such as taste masking, sustained and rapid release.
Effectively useful in low concentration (5-20%w/w).

Resins have high drug loading.Types of Ion-exchange Resins[1],[6],[8]There are two

major classes of ion-exchange resins(a) Cation and (b) Anion exchange resins.

Fig
1:Types of Ion exchange

Loading of drugs: Loading of drugs is done by two ways[3]

a)Column process:A highly concentrated drug solution is eluted through a bed or column of
the resin, until equilibrium is established.

b)Batch process:The resin particles are stirred with a large volume of concentrated drug
solution.Subsequently theresin is to be washed to remove adhering free and un-associated
drug and thereafter it is air dried.

Properties of ion exchange resins[1]

Particle size:The rate of ion exchange reactiondepends on the size of the resin particles.
Decreasing the size of the resin particle significantly decreases the time required for the
reaction to reach equilibrium with the surrounding medium. Porosity and swelling:
Theporosity of an ion-exchanger depends not only on the amount of cross-linking
substances used in polymerization but mainly on polymerization procedures. The structural
parameters considerably influence the swelling behaviour of the resin and consequently
have a marked effect on the release characteristics of drug resinates.The amount of swelling
is directly proportional to the number of hydrophilic functional groups attached to the
polymer matrix and is inverselyproportional to the degree of divinylbenzene cross-linking
present in the resin.
 Cross-linkage:The percentage of cross-linking affects the physicalstructure of the resin
particles. Resins with low degree of cross-linking can take up a considerable amount of
water and swell into a structure that is soft and gelatinous. However, resins with a high
divinyl benzene content swell very little, the particles take up only a small amount of water
and consequently are somewhat and brittle.

Available capacity:Thecapacity of an ion exchanger is a quantitative measure ofits ability

to take-up exchangeablecounter-ions and is therefore of major importance. However in the
preparation of drug resonates, the actual capacity obtained under specific experimental
conditions depends on the accessibility of the functional group for the drug of interest.

Acid base strength:Theacid base strength of an exchange is dependent on various

ionogenic groups, incorporated into the resin. Resin containing sulfonic, phosphonic or
carboxylic acid exchange groups have approximate pKa values of 1, 2-3 and 4-6,
respectively. Anionic-exchangers are quaternary, tertiary or secondary ammonium groups
having apparent pKa values of greater than 13, 7-9 or 5-9, respectively. The pKa value of
the resin will have a significant influence on the rate at which the drug will be released from
resinates in the gastric fluid.

Selectivity of the resins for the counter ion Factors other than size and charge also
contribute to the selection by an ion-exchange resin of one counter ion in preference to
another. The extent of sorption increases with i.The counter ion that, in addition to forming
a normal ionic bond with the functional group of an exchanger, also interacts through the
influence of Vander-Waalsforces with the resin matrix.ii.the counter ion least affected by
complex formation with its co-ion or non exchanging ion,iii.the counter ion thatinduces the
greater polarization. Stability: The resinous ion-exchangers are remarkably
inertsubstances. At ordinary temperature and excluding the more potent oxidising agents,
vinyl benzene cross-linked resins are resistant to decomposition through chemical attack,
but degeneration in the presence of storagegamma ray sources.

Purity and Toxicity: Thedrug resinates combinations contain 60% or more of the resins.
Commercial products cannot be used as such becausethey contain impurities that cause
toxicity. Therefore careful purification of the resin prior to treatment with the drug is
required.Applications in drug delivery systemThe use of ion exchange resins has occupied
an important place in the development of controlled or sustained release systems because of
their better drug retaining properties and prevention of dose dumping2. Sustained or
controlled release formulationsThe use of ion exchange resins for oral sustained release oral
formulations occupies important place. It has several advantages like:

Rate constant for drug absorption is less variable.

Readily controllable particle shape.

Release rate of drug from resinates is found to be more predictable.

Ion exchange resinates of drugs can help in reducing the dose.

Maintenance of drug concentrations below toxic level can be achieved.

Pharmaceutical applications [2]:Some Pharmaceutical applications of ion exchange

resins includes

Controlled/sustained drug delivery: Microencapsulated or coated

resinates:Microencapsulated of resinates provides better control over the drug release
because of the presence of a rate controlling membrane. The absorption of the drug from
coated resinates is a consequences of the counter ions into the coated resinates, release of
drug ions from the drug-resin complex by ion exchange process, and diffusion of drug ions
through the membrane into the surrounding absorption environment3, 4.

Drug release of the drug-resin complex and its microcapsules It is controlled by three
possible mechanisms

1.Mass or chemical reaction control: The exchange reaction between the counter ion and
drug.

2.Particle diffusion control: The release of drug through the porous within its particles.

3.Membrane diffusion control: The release of drug across the thin layer around the particle.

Pennkineticsystemsfurther modification of the coating of resinates for improved monitoring

of the drug release pattern. In this system, resinates is pre-treated with polyethylene glycol
to maintain the geometry and improve the coating process and also helps in controlling the
rate of swelling of the resinate matrix in water[11].

Cholesterol reducer: Cholestyramine resin USP, when used as an active ingredient, binds
bile acids; this leads to replenishment of bile acids; through increased metabolism of serum
cholesterol resulting in lowered serum cholesterol levels.Cholestryamine and cholestipol are
used in the treatment of type II hyperlipoproteinemia and familial hyperlipoproteinamia in
children and young adults.

Taste masking: Bitter cationic drugs can get adsorbed onto the weak cation exchange
resins of carboxylic acid functionallyto form the complex which is non bitter. Further
resinates can beformulated as dispersible tablets and mask the taste.Avari et al. reported
taste masking of highly bitter antibiotic, sparfloxacin with indion 204 weak cationic
exchanger[3],[25].

Improvement of tablet disintegration properties: Many tabletsdisintegrates owe their action

to capacity to absorb water and swell up. Fine particle size ion-exchange resins have shown
superiority as disintegration agents due to their considerable swelling pressures upon
hydration[25].

Improving the dissolution of poorly soluble drugs and Eliminating polymorphism:Drug

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

Improving stability:Complexing active ingredients with ion-exchange resins prevents

harmful interaction with other components like vitamin B12 and carboxylic acid this
complexes as effective as free drug. Ion exchange resins can also be used as carrier for
immobilized enzymes to provide extended activity at localized sites.

High purity of water: Therewill always be a need for purified water in the production of
pharmaceuticals. Water softening uses a cation exchange resin to exchange principally
calcium and magnesium ions for sodium ions and so prevent the formation of calcium
carbonate precipitates on reverse osmosis membranes.Therapeutic ApplicationsIon
exchange resins havefound use in the treatment of various pathological states such as
hyperacidity, treatment of ulcer;Na and K supplement depletion, nephrotic, pancreatic and
cardiac edema etc.Moreover, anion exchange resins have been used in the treatment of
hyperglycemias.Cholestyramine, aquaternary ammonium anion-exchange resin originally
was used to control pruritus in patients with elevated plasma bile acid concentrations.
Butpresently, it is recommended as an adjunctive therapy to patients with elevated serum
cholesterol. Another anion exchangeresin Colestipole hydrochloride acts by increasing
fractional carbolic rate of low density lipoproteins (LDL) thereby decreasing LDL.
Regulation of ion exchange resinsfor the food, water and beverage industriesThe FDA has
the responsibility to define conditions under which safe food additives may be used in the
production and preparation of foods and beverages.According to Section 25, use of ion
exchange resins under following conditions.i. The resins must be one of a preapproved
generic list of resincompositions (listed in 21 CFR 173.25); ii. The resins must be subjected
to pursuetreatment by the manufacture and/or user in accordance with the
manufacturer’sdirections; iii. The resins must be found to result in notmore than 1 part per
million organic extractives.