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Journal of Chemical and Pharmaceutical Research, 2015, 7(4):1436-1445

ISSN : 0975-7384
Review Article CODEN(USA) : JCPRC5

Ion exchange resins as drug delivery carriers

S. Sivaneswari*, D. Veena, P. Sai Sumana, P. Subhashree, L. Ramya, R. Rajalakshmi,
P. J. Chandana and E. Karthikeyan

College of Pharmacy, Sree Vidyanikethan Educational Institutions, Tirupati, Andhra Pradesh, India
_____________________________________________________________________________________________

ABSTRACT

Ion exchange resin(IER) are cross-linked synthetic high molecular weight solid water insoluble usually white or
yellowish, fabricated from organic polymer (polyelectrolyte) having ionizable functional group. IER have received
considerable attention from pharmaceutical scientists because of their versatile properties as drug delivery vehicles.
Research over the last few years has revealed that IER are equally suitable for drug delivery technologies, including
controlled release, transdermal, nasal, topical and taste masking. The major drawback of sustained release of
extended release or extended release is dose dumping, resulting in increased risk of toxicity. The use of IER 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 dumping. Synthetic ion exchange resins have been used in
pharmacy and medicine for taste masking or controlled release of drug. Drug resin complexation converts drug to
amorphous form leading to improved drug dissolution. Several studies have reported the use of IER for drug
delivery at the desired site of action. Sulfonated and carboxylic resins with a polystyrene backbone are most widely
used in clinical medicine.

Keywords: Ion exchange resins, taste masking, resin drug complex, controlled release
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INTRODUCTION

IER is defined as “Ion exchange resin are cross-linked synthetic high molecular weight solid water insoluble usually
white or yellowish, fabricated from organic polymer (polyelectrolyte) having ionisable functional group”. Novel
drug delivery systems are gaining momentum in the recent two decades as these results in reduced frequency of
dosing and patient compliance. Intensity and duration of action has been the subject of increasing multidisciplinary
research. One of the attractive methods for modified drug delivery systems is the use of ion exchange resins (IER) as
carriers for such systems [1]. Complexes between IER and drugs are known as ion exchange resinates, which have
been used in pharmaceutical formulations for several decades.

The principle of IER at which it acts is that it is a reversible process that exchanges their mobile ion of equal charge
with the surrounding insoluble organic polymer having charged functional site. IER are insoluble polymers that
contain acidic or basic functional groups and have the ability to exchange counter-ions within aqueous solutions
surrounding them. An ion exchange resin is exhibited like small bead with a diameter between 1-2 mm. It is usually
white or yellowish and it is fabricated from an organic polymer substrate backbone. Ion exchange is a reversible
process in which ions of like sign are exchanged between liquid and solid when in contact with a highly insoluble
body. The drug is released from resinate by exchanging with ions in the gastrointestinal fluid, followed by drug
diffusion. Due to the presence of high molecular weight water insoluble polymers, the resins are not absorbed by the
body and are therefore inert. IER have specific properties like available capacity, acid base strength, particle size,
porosity and swelling, on which the release characteristics of drug resonates are dependent. Drug resinates are
generally prepared with purified resins and appropriate drugs [2-4].

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Research over the last few years has revealed that IER are equally suitable for drug delivery technologies, including
controlled release, transdermal, nasal, topical and taste masking. Synthetic ion exchange resins have been used in
pharmacy and medicine for taste masking or controlled release of drug as early as 1950[5-6]. Ion-exchange systems
are advantageous for drugs that are highly susceptible to degradation by enzymatic process. A major advantage of
ion exchange system is low running cost. It requires little energy and the regenerated chemicals are cheap.
Furthermore, if well maintained, resin beds can last for many years before replacement. However, the limitation is
that the release rate is proportional to the concentration of the ions present in the area of administration. More so, the
release rate of drug can be affected by variability in diet, water intake and individual intestinal content.

1.1.Advantages [7]
• Eliminate over or under dosing
• Maintain drug levels in desired range
• Increased patient compliance
• Need for less dosing
• 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 and probability of dose dumping.

1.2.Clinical Advantages
• Reduction in frequency of drug administration
• Improved patient compliance
• Reduction in drug level fluctuation in blood
• Reduction in drug accumulation with chronic therapy
• Reduction in drug toxicity (local/systemic)
• Stabilization of medical condition (because of more uniform drug levels)
• Improvement in bioavailability of some drugs because of spatial control
• Economical to the health care providers and the patient

1.3.Disadvantages [8]
• Reduced potential for dose adjustment.
• Cost of single unit higher than conventional dosage forms.
• Increase potential for first pass metabolism.
• Requirement for additional patient education for proper medication.
• Decreased systemic availability in comparison to immediate release conventional dosage forms and poor in vitro
and in vivo correlations.

2.Structure and Chemistry of Ion Exchange Resin

IER are simply insoluble polyelectrolyte’s that are insoluble polymers which contain ionisable groups distributed
regularly along the polymer backbone. The most common resins used in formulations are cross-linked polystyrene
and polymethacrylate polymers [8]. When IER are mixed with a fluid such as water, ions in the fluid can exchange
with the polyelectrolyte’s counter ions and be physically removed from the fluid.

An ion exchange resin is a polymer (normally styrene) with electrically charged sites at which one ion may replace
another. There are numerous functional groups that have charge, only a few are commonly used for man-made IER.
These are:

• -COOH, which is weakly ionized to -COO¯ ,

• -SO3H, which is strongly ionized to -SO3¯ ,
• -NH2, which weakly attracts protons to form NH3+,
• -secondary and tertiary amines that also attract protons weakly,
-NR3+, which has a strong, permanent charge (R stands for some organic group).

These groups are sufficient to allow selection of a resin with either weak or strong positive or negative charge.

3.Types of Ion-exchange Resins

There are two major classes of ion-exchange polymers [9] (Fig. 1)

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(a) Cation and (b) anion exchange resins. These are discussed in the following two sub-sections.

Fig. 1. Classification of IER.

3.1.Cation exchange resins
Cation exchange resins contain covalently bound negatively charged functional groups and exchanges positively
charged ions. They are prepared by the copolymerization of styrene and divinyl benzene and have sulfonic acid
groups (-SO3H) introduced into most of the benzene rings. The mechanism of cation exchange process can be
represented by the following reaction in Eq. (1)

R- - ex+ + C+ →R- - C+ +ex+ (1)

where, R is a resin polymer with SO3- sites available for bonding with exchangeable cation (ex+), and C+ indicates
a cation in the surrounding solution getting exchanged.

Cation exchange resins can be further classified into

(a) strong acid cation exchange resins and (b) weak acid cation exchange resins.
3.1.1.Strong acid cation exchange resins
The chemical behaviour of these resins is similar to that of a strong acid. These resins are highly ionized in both the
acid (R-SO3H) and salt (RSO3Na) form of the sulfonic acid group (-SO3H). They can convert a metal salt to the
corresponding acid by the reaction in Eq. (2):
2(R-SO3H) + NiCl2 → (R-SO4) Ni + 2HCl (2)

The hydrogen and sodium forms of strong acid resins are highly dissociated, and the exchangeable Na+ and H+ are
readily available for exchange over the entire pH range. Consequently, the exchange capacity of strong acid resins is
independent of the solution pH .

3.1.2.Weak acid cation exchange resins

These resins behave similarly to weak organic acids that are weakly dissociated. In a weak acid resin the ionisable
group is a carboxylic acid (COOH) as opposed to the sulfonic acid group (SO3H) used in strong acid resins. The
degree of dissociation of a weak acid resin is strongly influenced by the solution pH. Consequently, resin capacity
depends in part on the solution pH. A typical weak acid resin has limited capacity below a pH of 6.0, making it
unsuitable for deionizing acidic metal finishing wastewater.

3.2.Anion exchange resins [10]

Anion exchange resins have positively charged functional groups and they exchanges negatively charged ions.
These are prepared by first chlormethylating the benzene rings of styrene-divinylbenzene copolymer to attach
CH2Cl groups and then causing these to react with tertiary amines such as triethylamine. The mechanism of anion
exchange process can be represented by the following reaction in Eq. (3)

R+ - ex - + A- → R+ - A- + ex- (3)

where, R+ indicates a resin polymer with number of sites available for bonding with exchangeable anion (ex-), and
A- indicates cations in the surrounding solution getting exchanged. Anion exchange resins can be further classified
into two which are as follows:

3.2.1.Strong base anion exchange resins

Strong base resins are highly ionized and can be used over the entire pH range. These resins are used in the
hydroxide (OH) form for water deionization. They will react with anions in solution and can convert an acid solution

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to pure water Eq. (4)

R-NH3OH + HCl → R-NH3Cl + H2O (4)

Regeneration with concentrated sodium hydroxide (NaOH) converts the exhausted resin to the OH form.

3.2.2.Weak base anion exchange resin

Weak base resins are like weak acid resins in that the degree of ionization is strongly influenced by pH. Hence,
weak base resins exhibit minimum exchange capacity above a pH of 7.0. The weak base resin does not have an OH
ion form as does the strong base resin Eq. (5)

R-NH2 + HCl → R-NH3Cl (5)

Consequently, regeneration needs only to neutralize the absorbed acid; it need not provide OH ions. Less expensive
weakly basic reagents such as ammonia (NH3) or sodium carbonate can be employed.

A typical cation-exchange resin is prepared by the copolymerization of styrene and divinylbenze. During the
polymerization, polystyrene formed as a linear chains and these become covalently bonded to each other by
divinylbenze cross links. If sulphuric acid is then allowed to react with this copolymer, sulphonic acid groups are
introduced into most of the benzene rings of the styrene-divinylbenze polymer, and the final substance formed is
known as cation-exchange resin.

A typical anion exchange resin is prepared by first chloromethylating the benzene rings of the three dimensional
styrene-divinylbenzene copolymers to attach – CH2Cl groups and then causing these to react with a tertiary amine,
such as trimethylamine. This gives the chloride salt of strong-base exchanges.

4.Role of IER in Controlled Drug Delivery Systems

The major drawback of controlled release is dose dumping, resulting in increased risk of toxicity. The usage of IER
during the development of controlled release formulations plays a significant role because of their drug retarding
properties and prevention of dose dumping. The drug resinates can also be used as a drug reservoir, which has
caused a change of the drug release in hydrophilic polymer tablets [11].

The use of IER into drug delivery systems have been encouraged because of their physico-chemical stability, inert
nature, uniform size, spherical shape assisting coating and equilibrium driven reproducible drug release in ionic
environment. The physical and chemical properties of the IER will release the drug more uniformly than that simple
matrix formulation [12]. Drug molecules attached to the resins are released by appropriate charged ions in the
gastrointestinal tract, followed by diffusion of free drug molecules out of the resins as shown below in Eqs. (6) and
(7):

Resin- Drug+ + X+ Resin-....X+ + Drug+ (6)

՜
՜ Resin+...X- + Drug-
Resin+ Drug-+ X- (7)

where, X and Y are ions in the gastrointestinal tract.

IER have been used as drug carriers in pharmaceutical dosage forms for controlled release formulation [13-16]. The
prolonged release of the active drug is accomplished by providing a semi-permeable coating around discrete,
minute, ion exchange resin particles with which the drug component has been complexed to form an insoluble drug
resin complex. The semi-permeable coating creates a diffusion barrier and the thickness of which can be adjusted to
provide the desired level of retardation of drug availability in the gastrointestinal tract over a period of time. Several
preparations involving strong resinates of sulphuric 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 micro particles [17-20].

5.Method of Preparation
The important step in the preparation of drug resinates is to purify the resins. Purification of resin can be achieved
by washing with absolute ethanol, ethanol and water mixture. Final washing with water removes all the impurities.
Purification is generally done by cycling repeatedly between the sodium and hydrogen forms with a cation

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exchanger or between the chlorides and hydroxide forms with a anion exchangers. The conversion can be achieved
by soaking the resins with acid or alkali solutions, respectively. After changing the ionic form, the resin is subjected
to washing with distilled water until elute becomes neutral in reaction, and finally is dried at 50ºC. The drugs are
loaded on to the resins by column method and batch method [21-23].

5.1.Column Method: Highly concentrated drug solution is passed through the column containing resins. Maximum
efficiency is best obtained by the column method.

5.2.Batch Method: In this method the drug solution is agitated with a quantity of resin until equilibrium is attained.
Subsequently the resin is to be washed to remove free and un-associated drug and thereafter it is air dried.

Fig 2. The mechanism of action of the drug release from the ion exchange resin

6.Mechanism and Principle

Anion exchange resins involve basic functional groups capable of removing anions from acidic solutions while
Cation exchange resins contain acidic functional group, capable of removing cations from basic solutions[21-22].

The use of IER to prolong the effect of drug release is based on the principle that positively or negatively charged
pharmaceuticals, combined with appropriate resins to yield insoluble polysalt resinates.

R-SO-3 H+ + H2N-A ↔ R-SO-3 – H3N-A

R-N+H3OH- + HOOC-B ↔ R-N+H3 –OOC-B+H2O

H2N-A → basic drug, R-SO-3H+ → cation exchanges, HOOC-B → acidic drug

R-NH3+OH- → anion exchange resins.

In The Stomach:
1) Drug resinate + HCl ↔ acidic resin + drug hydrochloride
2) Resin salt + HCl ↔ resin chloride + acidic drug

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In The Intestine:
1) Drug resinate + NaCl ↔ sodium resinate + drug hydrochloride
2) Resin salt + NaCl ↔ resin chloride + sodium salt of drug

This system incorporates a polymer barrier coating and bead technology in addition to the ion exchange mechanism.
The initial dose comes from an uncoated portion, and the remainder from the coated beads. The coating is not
dissolved and coating is extended over 12-hour period by ionic exchange. The drug-containing polymer particles are
minute, and may be suspended to produce a liquid with extended release characteristics as well as solid dosage
forms .

EXAMPLE:
Examples of drug product of this type include;
1) Hydrocodone polistirex and chlorpheniramine polistirex suspension [Tussionex Pennkinetic Extended Release
Suspension (Medeva)] and
2) Phentermine resin capsules [Ionamin Capsules (Pharmanex)].

7.Important Properties of IER[23-30]

7.1.Crosslinkage
The amount of crosslinking depends on the proportions of different monomers used in the polymerization step.
Practical ranges are 4 % to 16 %. Resins with very low crosslinking tend to be watery and change dimensions
markedly depending on which ions are bound.

7.2.Moisture Content
A physical property of the ion exchange resins that changes with changes in crosslinkage is the moisture content of
the resin. For example sulfonic acid groups attract water, and this water is tenaciously held inside each resin particle.
The quaternary ammonium groups of the anion resins behave in a similar manner.

7.3.Capacity
The total capacity of an ion exchange resin is defined as the total number of chemical equivalents available for
exchange per some unit weight or unit volume of resin. The capacity may be expressed in terms of milliequivalents
per dry gram of resin or in terms of millequivalents per milliliter of wet resin. The more highly crosslinked a resin,
the more difficult it becomes to introduce additional funcitonal groups. Sulfonation is carried out after the
crosslinking has been completed and the sulfonic acid groups are introduced inside the resin particle as well as over
its surface. Likewise, the quaternary ammonium groups are introduced after the polymerization has been completed
and they too are introduced both inside the particle as well as on its surface. Fewer functional groups can be
introduced inside the particles when they are highly crosslinked and hence the total capacity on a dry basis drops
slightly.

This situation is reversed when a wet volume basis is used to measure the capacity on a resin. Although fewer
functional groups are introduced into a highly crosslinked resin, these groups are spaced closer together on a volume
basis because the volume of water is reduced by the additional crosslinking. Thus the capacity on a wet volume
basis increases as cross-linking increases.

7.4.Equilibration Rate
Ion exchange reactions are reversible reactions with equilibrium conditions being different for different ions.
Crosslinkage has a definite influence on the time required for an ion to reach equilibrium. An ion exchange resin
that is highly crosslinked is quite resistant to the diffusion of various ions through it and hence, the time required to
reach equilibrium is much longer. In general, the larger the ion or molecule diffusing into an ion exchange particle,
or the more highly crosslinked the polymer, the longer will be the time required to reach equilibrium conditions.

7.5.Summary of Crosslinkage Effects

Copolymers of styrene containing low amounts of divinylbenzene (1-4%) are characterized as follows
• High degree of permeability
• Contain a large amount of moisture
• Capacities are lower on a wet volume basis
• Equilibrium rates are high
• Physical stability is reduced

Selectivity for various ions is decreased, but ability to accommodate larger ions is increased. Copolymers of styrene
containing high amounts of divinylbenzene (12-16%) exhibit characteristics in the opposite direction.

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7.6.Particle size[31]
The physical size of the resin particles is controlled during the polymerization step. Screens are used to sieve resins
to get a fairly uniform range of sizes. Mesh sizes in the following table refer to U.S. Standard screens. A higher
mesh number means more and finer wires per unit area and thus a smaller opening.
Table 1 Particle size of resins

Mesh Range Diameter of Particles

Inches Micrometers
20 – 50 0.0331-0.0117 840-297
50 – 100 0.0117-0.0059 297-149
100 – 200 0.0059-0.0029 149-74
200 – 400 0.0029-0.0015 74-38
minus 400 < 0.0015 < 38

7.7.Flow Rate
Ion exchange processes are usually carried out in columns with the resin resting on a suitable support. Liquids may
be processed either up-flow or down-flow through such columns. The spherical particles of ion exchange resin resist
the flowing of a liquid through or around them. The smaller the particle size, the greater will be this resistance
against which a liquid must flow. This resistance goes up very rapidly when particles smaller than 100 mesh are
employed[32].

8.Evaluation of Drug Resinates[33-39]

The invitro test demonstrates the release pattern of a drug from resinate preparation dosage form. It depends on size
of resinate, degree of cross linkage of resin with drug, nature of the resins, nature of the drug and test conditions that
is ionic strength of the dissolution medium. In vivo procedures used for estimating drug activity of resinates include
serum concentration level determination, urinary excretion, and toxicity studies. Bioavailability of drug from drug-
resinate complexes depends on both transit of the particles through the gastrointestinal tract and drug release
kinetics. The complex will release the active content only when it replaced by the ion which has the same charge.
Since the exchange is an equilibrium process, it will depend on the ionic constitution and the fluid volume of the
body fluid. In additional, release is not instantaneous, and the drug must diffuse through the resin from the internal
exchange sites. Thus, agitation and time of exposure play a key role in drug release.

Stomach emptying with fine particles, likely follows a first order or distributional process. In the intestine, the
neutral pH should keep all ionic sites ionized, and the exchange process should occur continuously. The absorption
into the body of solubilised drug should drive the equilibrium further toward drug release. In the large intestine,
desorption from resins and absorption into the body may be slowed considerably due to low fluid content,
entrapment in faecal matter, and poor absorption in colon. The highly insoluble resin never dissolves, and should not
be absorbed. It will simply be eliminated from the body with whatever counter-ions have replaced the drug.

9.Applications of IER [39-45]

9.1.Pharmaceutical applications
Some pharmaceutical applications of IER include

9.2.Taste masking
Masking of bitter taste in active principal ingredients in oral formulations posses a major challenge to
pharmaceutical industry especially for paediatric and geriatric patients. Masking of the unpleasant taste of a drug
improves compliance and product value. Amongst the numerous available taste-masking methods, ion exchange
resins are inexpensive and can be used to develop. Previously some workers used carbomer to mask the nauseating
and unpleasant taste of erythromycin and clarithromycin, by adsorption into Carbopol and then encapsulating the
resulting particles with hydroxylpropyl methylcellulose phthalate.

9.3.Eliminating polymorphism
Many pharmaceutical solids can exist in different physical forms. Polymorphism is often characterized as the ability
of a drug substance to exist as two or more crystalline phases that have different arrangements and/or conformations
of the molecules in the crystal lattice. This is a common problem in the pharmaceutical industry and huge sums of
money are spent trying to identify polymorphs and trying to make stable, suitably soluble forms. Failure to resolve
such a problem can result in significant stability and stability problems for the final dosage form. Ion exchange
resins present a unique way to deal with the problem because using resinates completely eliminates any problem
with polymorphism.

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9.4.Improving the dissolution of poorly soluble drugs
Ion exchange drug resinate complexes can be used to enhance the dissolution rate of a poorly soluble drug. Using
micronization to increase the rate of dissolution can be problematic, because it frequent requires specialized
equipment and often there can be agglomeration of the fine particles after grinding. The grinding can also result in
melting and conversion to other crystal forms. These problems are completely eliminated by using the ion exchange
resin approach.

9.5.Improving stability
The drug resinate is frequently more stable than the original drug. For instance, vitamin B12 has a shelf-life of only a
few months while it’s resinate has more than two years. Another example is nicotine which discolors on exposure to
air and light, but the resinate used in manufacturing nicotine chewing gums and lozenges is much more stable.

9.6.Improving physical characteristics

Most drug substances are in solid form there are some that are liquids or difficult-to-handle solids. Because the
physical properties of the resinates are similar to the resin not the drug, the resinates of these drugs will be free-
flowing solids. A very well established example of this is the nicotine resinate used in nicotine chewing gums and
lozenges. Nicotine is in liquid form but its resinate is a stable, free- flowing solid. The resins have a uniform,
macroreticular morphology that provides excellent flow ability to the formulation.

9.7.Drug delivery applications [46-49]

9.7.1.Oral drug delivery: The major drawback of sustained release or extended release is dose dumping hence
resulting in increased risk of toxicity. The use of IER has occupied an important place in the development of
controlled or sustained-release systems due of their better drug retaining properties and prevention of dose dumping.
The drug resinates can also be used as a drug reservoir, which has caused a change of the drug release in hydrophilic
polymer tablets. The use of ion exchange resins into drug delivery systems have been encouraged because of their
physico-chemical stability, inert nature, uniform size, spherical shape assisting coating and equilibrium driven
reproducible drug release in ionic environment.

9.7.2.Nasal drug delivery: A novel nasal formulation, in the form of a nicotine-Amberlite resin complex powder, has
been developed that provided an optimal combined pulsatile and sustained plasma nicotine profile for smoking
cessation. Amberlite IRP69 and Amberlite IR120 are similar cationic exchange materials with the same ion
exchange capacity but due to a smaller particle size range (10-150 µm). Amberlite IRP69 had a better flow property
and a better adsorptive capacity than Amberlite IR120. The nicotine plasma profiles demonstrated that an initial
rapid peak plasma level of nicotine followed by a sustained elevated level could be achieved by adjusting the ratio of
free to bound nicotine in the Amberlite powder formulation.

9.7.3.Transdermal drug delivery: IER are also involved in the formulation of transdermal drug delivery systems.
The release rates of ketoprofen from the carbopol-based gel vehicles containing ion exchange fibers to which the
ketoprofen had been bound were determined across 0.22 µm microporous membrane. The fluctuation of the release
rate of ketoprofen from the vehicles was much lower compared with that of simple gels, though the cumulative
amount of ketoprofen delivery was less. In addition ions could increase the rate and extent of ketoprofen delivery.

9.7.4.Ophthalmic drug delivery: IER also find application in opthalamic drug delivery systems. An example is
Betoptic S which is a sterile ophthalmic suspension and it contains 0.25% betaxolol hydrochloride. It is a
cardioselective beta-adrenergic receptor blocking agent manufactured by Alcon Laboratories in the US. It is an
ocular resinate ophthalmic product designed to lower elevated intraocular pressure. The drug resinate complex is
formed when the positively charged drug is bound to a cation ion-exchange resin (Amberlite1 IRP 69). The 0.25%
ophthalmic suspension of the drug showed an increased bioavailability.

10.Diagnostic and therapeutic applications

Synthetic as well as natural polysaccharides based on ion-exchange resins have been used with good results for
diagnostic determinations. eg. In gastric acidity. They have also found applications as adsorbents of toxins, as
antacids, and as bile acid binding agents. Ion-exchange resins have been successfully used therapeutic in the
treatment of liver diseases, renal insufficiency, urolithic disease and occupational skin disease. For instance, sodium
polystyrene sulfonate is a sulfonic cation-exchange resin used in the treatment of hyperkalemia and also used in
acute renal failure. Phenteramine, a sympathomimetic amine is indicated for short term use in the management of
exogeneous obesity in a regimen of weight reduction utilizing caloric restriction. It also has application in the
control of cholesterol and potassium ion levels.

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11.Some IER Available in the Market
The use of IER to form drug adsorbates for sustained release [50-53] was closely associated with Strasenburgh
Laboratories, an affiliate of Pennwalt Corporation, which was granted several patents in this area. Their first
significant application involved amphetamine adsorbed onto a sulfonic acid cation exchange resin (Biphetamine)
which is use in appetite suppression and for also for behavior control in children. The drug is administrated once or
twice daily. Other products that have been introduced commercially since the initial work with amphetamine include
Penntuss which is a combination of Codeine and Chlorpheniramine. This is a liquid suspension used as a cough
suppressant and relief of cold. It is taken twice daily. Both drugs are bound to a sulfonic acid cation-exchange resin.
The chlorpheniramine-resinates are uncoated due to much high affinity for the resin while the codeine-resinates are
coated with ethylcellulose. Other products used for cough and cold include phenylpropanolamine, chlorpheniramine,
and dextromethorphan. Some other examples include Ionamin (phentermine) and Tussionex (hydrocodone polistirex
and chlorpheniramine polistirex) both are marketed by Medeva Pharmaceuticals, Inc.) .

CONCLUSION

IERs have been used in pharmacy and medicine for various functions, which include tablet disintegration,
bioadhesive systems, sustained release systems. In recent years IER have been successfully utilized for masking of
taste of bitter drugs.IER play a major role in the modification of drug release by forming a complex with drug
substances.

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