ISSN: 0975-8232

IJPSR (2010), Vol. 1, Issue 4

(Review Article)

Received 10 February, 2010; received in revised form 20 March, 2010; accepted 25 March, 2010

TASTE MASKING BY ION EXCHANGE RESIN AND ITS NEW APPLICATIONS: A REVIEW
V. K. Suhagiya*, A. N. Goyani and R. N. Gupta
Department of Pharmaceutical Sciences,Birla Institute of Technology, Mesra, Ranchi (Jharkhand), India
Keywords:
Taste Masking,
Ion Exchange resin,
Bitter Drugs,
Amberlite IRP,
Indion,
Tulsion,
Kyron

*Correspondence for Author

Vishal K. Suhagiya
Department of Pharmaceutical
Sciences,
Birla Institute of Technology,
Mesra, Ranchi Jharkhand, India
E-mail: vishusuhagiya@gmail.com

ABSTRACT
More than 50% of pharmaceutical products are orally
administered for several Reasons and undesirable taste is one
of the important formulation problems that is Encountered
with such oral products. Taste of a pharmaceutical product is
an important parameter governing compliance. Hence taste
masking of oral Pharmaceuticals has become important tool to
improve patient compliance and the Quality of treatment
especially in paediatrics. Different methods have been
suggested for Masking of taste of bitter drugs, which includes,
coating of drug particles with inert agents, taste masking by
formation of inclusion complexes, molecular complexes of
drug with other chemicals, solid dispersion system,
microencapsulation, multiple emulsions, using liposome's,
Prodrugs and mass extrusion method but ion exchange resin is
one of most extensively Used method to overcome this
problem. Ion-exchange resins (IER) have received considerable
attention from pharmaceutical scientists because of their
versatile properties as drug-delivery vehicles. In the past few
years, IER have been extensively studied in the development
of novel drug-delivery systems (DDSs) and other biomedical
applications. Also Recently the New Applications of Ion
Exchange Resin like Opthalmic Drug Delivery, AntiDeliquescence, Improve Solubility, and Polymorphism has
confirmed. This review highlights complete account of ion
exchange resin and its application in drug delivery research
are-discussed.

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INTRODUCTION: One of the popular

approaches in the taste masking of bitter
drugs is based on Ion Exchange resin (IER).
IER are solid and suitably insoluble high
molecular weight poly- electrolytes that
can exchange their mobile ions of equal
charge with the surrounding medium.
Synthetic ion exchange resins have been
used in pharmacy and medicine for taste
masking or controlled release of drug as
early as 19501. Being high molecular
weight water insoluble polymers, the
resins are not absorbed by the body and
are therefore inert2. The long-term safety
of ion exchange resins, even while
ingesting large doses as in the use of
cholestyramine to reduce cholesterol is an
established unique advantage of IER due
to the fixed positively or negatively
charged functional groups attached to
water insoluble polymer backbone. These
groups have an affinity for oppositely
charged counter ions, thus absorbing the
ions into the polymer matrix.
Since most drugs possess ionic
sites in their molecule, the resin's charge
provides a means to loosely bind such
drugs and this complex prevents the drug
release in the saliva, thus resulting in taste
masking. For taste masking purpose weak
cation exchange or weak anion exchange
resins are used, depending on the nature
of drug. The nature of the drug resin
complex formed is such that the average
pH of 6.7 and cation concentration of
about 40meq/L in the saliva are not able
to break the drug resin complex but it is
weak enough to break down by
hydrochloric acid present in the stomach.
Thus the drug resin complex is absolutely
tasteless with no after taste, and at the
same time, its bioavailability is not
affected3. IER have received considerable

attention from pharmaceutical scientists

because of their versatile properties as
drug delivery vehicles. In past few years,
IER have been extensively studied in the
development of Novel drug delivery
system and other biomedical applications.
Several IER products for oral and peroral
administration have been developed for
immediate release and sustained release
purposes. Research over the last few
years has revealed that IER are equally
suitable for drug delivery technologies,
including controlled release, transdermal,
site-specific,
fast
dissolving,
iontophoretically assisted transdermal,
nasal, topical and taste masking systems.
POLYMER MATRIX: The most commonly
used polymer backbone for anion
exchange and strong cation exchange
resin
is
based
on
polystyrene.
Divinylbenzene (DVB) is included in the
copolymerization for cross linking the
polymer chains. The amount of DVB,
usually expressed as percentage by weight
has a strong effect on the physical
properties. The weak cation exchange
resins are generally polyacrylic or
polymethacrylic acids with DVB as cross
linking agents depending on the presence
of ions4. Four major types of ion exchange
resins are available which are summarized
in Table 1.
CLASSIFICATION OF ION EXCHANGE
RESINS (IER): The various ion exchange
materials available can be classified as
shown in Fig. 1 on the basis of nature of
structural and functional components and
ion exchange Process. Ion exchange resins
contain positively or negatively charged
sites and are accordingly classified as
either cation or anion exchanger.

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International Journal of Pharmaceutical Sciences and Research

Table
Type

1:

Common

ion

exchange

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resin

Exchange
species

Polymer backbone

Commercial Resins

-SO3H

Polystyrene DVB

Amberlite IR 120, Dowex 50, Indion 244, Purolite C100HMR, Kyron-T154

-SO3Na

Sodium Polystyrene

Tulsion T-344, Amberlite IRP 69, Indion 254

Strong
cation

-COOH
Weak
cation

Amberlite IRC 50, Indion 204, Purolite C102DR, Kyron-T-104, Kyron-T114, Doshion P544(R), Tulsion T-335

-COO-K

Methacrylic acid DVB

Tulsion T-339, Amberlite IRP88, Indion 234, Kyron-T-134

Strong
anion

N R3

Polystyrene DVB

Amberlite IR 400, Dowex 1,

Indion 454, Duolite AP 143

Weak
anion

N R2

Polystyrene DVB

Amberlite IR 4B, Dowex 2

Figure 1: Classification of ion exchange resins

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International Journal of Pharmaceutical Sciences and Research

Within each category, they are

further classified as inorganic and organic
resins. The functional group in cation
exchanger
and
anion
exchanger
undergoes reaction with the cations and
anions of the surrounding solution
respectively. The strong cation exchanger
contains sulphuric acid sites [Dowex-50]
whereas
weak
cation
exchangers
[Amberlite IRC-50, Indion 204] are based
on carboxylic acid moieties. The strong
anion exchange resins [Dowex-1] have
quaternary amine ionic sites attached to
the matrix, whereas weak anion
exchanger [Amberlite IR 4B] has
predominantly
tertiary
amine
substituents. Inorganic and organic
exchange resin is further categorized into
synthetic, semi-synthetic and natural
depending on their source4.
SELECTION OF SUITABLE ION EXCHANGE
RESIN: The selection of IER for drug
delivery applications is primarily governed
by the functional-group properties of the
IER5. However, the following points need
to be considered during selection:
Capacity of the IER [i.e. the
concentration of the exchangeable
group in the resin, usually expressed in
mill equivalents per gram (meq g1) of
dry resin];
Degree of cross linking in the resin
matrix;
Particle size of resin;
Nature of drug and site of drug delivery.
It is also important to evaluate the resin
in the
pH- and ionic-strength
environment, simulating the in vivo
situation;
Swelling ratio;
Biocompatibility and biodegradability;
Regulatory status of the IER.

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For example, a low degree of cross

linking of the resin will facilitate the
exchange of large ions, but it will also
cause volume changes in the resin upon
conversion from one form to another.
Similarly, the use of a strong IER will give a
rapid rate of exchange, but it could also
cause hydrolysis of the labile drugs
because strong IER are effective acid-base
catalysts. Therefore, a fine balance of all
the parameters needs to be made to
achieve optimal performance of drugdelivery systems (DDSs) containing IER.
CHARACTERIZATION OF IER: As the
performance of DDSs depends on the
quality of IER, it is important to evaluate
IER at each stage of the preparation of
resinates. The following parameters are
generally evaluated:
Particle size measured directly with a
set of micro sieves by screening6. The
particle size of IER can also be
determined by microscopy, Coulter
counter 7 and other available
techniques.
Porosity the porosity of dry IER can be
determined
through
nitrogen
adsorption at 195C, and by measuring
the
true
density
(mercury
displacement)8.
Scanning
electron
Microscopy reveals the internal pore
structure. The use of an air-compression
pycnometer for the determination of
porosity has also been reported in the
literature9.
Moisture content determined by Karl
Fischer titrimetry. Excess water can be
removed
by drying in vacuum
desiccators10.
IE capacity the IE capacity of strong
CER is determined as meq g1 by
evaluating the number of moles of Na+,
which are absorbed by 1 g of the dry

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International Journal of Pharmaceutical Sciences and Research

resin in the hydrogen form11, 12 Similarly,

the IE capacity of a strong basic AER is
evaluated by measuring the amount of
Cl taken up by 1 g of the dry resin in the
hydroxide form.
MECHANISM OF BINDING OF ION
EXCHANGE RESIN WITH DRUGS: The
principle property of resins is their
capacity to exchange bound or insoluble
ions with those in solution. Soluble ions
may be removed from solution through
exchange with the counter ions adsorbed
on the resin as illustrated in equation 1
and 2.

Re-So3 Na + Drug
Re-SO3 Drug
+
+ Na .......................................................1

Re-N (CH3) + Cl + Drug

Re-N (CH3)
+

Drug + Cl ............................................2
These exchanges are equilibrium reactions
in which the extent of exchange is
governed by the relative affinity of the
resins for particular ions. Relative affinity
between ions may be expressed as a
selectivity co-efficient derived from mass
action expression13 given in equation no.
3.
[D]R [M]S
KDM= -------------[D]S [M]R
Where,
[D]R = Drug concentration in resin
[D]S = Drug concentration in the solution
[M]S = Counter ion concentration in the
solution
[M]R = Counter ion concentration in the
resin

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Factors that influence selectivity include

valency, hydrated size, pKa and the pH of
the solutions.
Borodkin et al. used selectivity
coefficient to express the interaction of
eleven amino drugs with potassium salt of
polacrin, a polycarboxylic acid resin. When
loading of resin with an ion of less affinity,
the exchange may be driven towards the
direction of unfavorable equilibrium by
flooding the influence with high
concentration
or
by
using
3
chromatographic column procedures .
RESINATE PREPARATION: Once the
selection of a resin is made, the next step
involves preparing its complex with drug,
before designing a suitable delivery
system. The main hurdle is to optimize the
conditions of preparation, in order to
obtain the desired drug loading in the
resinates. Generally, the following steps
are involved in the preparation of
resinates:
Purification of resin by washing with
absolute ethanol, ethanol and water
mixture14. Final washing with water
removes all the impurities.
Changing the ionic form of IER might
occasionally be required to convert a resin
from one form to another, if it does not
have the desired counter ions15. Strongly
acidic CER are usually marketed in Na+
form and strongly basic AER in Cl form.
They are
generally converted into
hydrogen
and
hydroxide
forms,
respectively. 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

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International Journal of Pharmaceutical Sciences and Research

until elute becomes neutral in reaction,

and finally is dried at 50C.
Preparation of resinate is normally done
by two techniques:

Batch technique after suitable

pretreatment, a specific quantity of
the granular IER
is agitated with
the drug solution until the
equilibrium is established16 and;

Column technique resinate is

formed by passing a concentrated
solution of drug through the IERpacked column until the effluent
concentration is the same as the
eluent concentration.
DRUG RELEASE FROM IER:
The rate and completeness of drug
desorption
in-vivo
will
be
controlled by the diffusion rate of
the drug through the polymer
phase of the resin,(usually a
function of molecular weight),the
selectivity of the drug for the resin
,and the concentration of the
electrolytes particularly in the
hydrogen ion, in the desorption
environment17.
More hydrophobic drugs will
usually elute from the resin at a
lower rate, as will drugs with a
relatively high selectivity for the
carboxylic acid functional structure
In the resin other resin-sorbate
interactions are possible, and
these can have a pronounced
effect upon loading capacities and
rates.
An example of this might be the
presence of the transition metal in
the structure of the sorbate
molecule which can result in

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considerable selectivity through

the formation of a coordination
compound with the resin.
PROPERTIES OF IER:
1. EXCHANGE CAPACITY: The capacity of
an ion exchanger is a quantitative
measure of its ability to take up
exchangeable Counter-ions and refers to
the number of ionic groups per unit
weight or volume (meq per g or meq per
mL). The weight-based value is generally
much greater than the volume-based
value since the resin is highly hydrated.
However, in preparing drug resinates,
the actual capacity obtainable under
specic experimental conditions would
depend upon the accessibility of the
functional groups for the drug of interest.
The so-called available capacity will be
related to the drug physicochemical
properties and will be inferior to the total
capacity. The exchange capacity may limit
the amount of drug that may be sorbed
onto a resin and the potency of a drug
resin complex. Weak cation exchangers
derived from acrylic acid polymers have
higher exchange capacity (~10 meq/g)
than the sulfonic acid (~4 meq/g) or
amine resins because of bulkier ionic
substituents and the polystyrene matrix.
Therefore, higher drug loads may often be
achieved with the carboxylic acid resins18.
2. CROSS-LINKAGE: The degree of crosslinking depends on the percent DVB used
in the copolymerization. The Ion-exchange
products available today are limited to a
range of 216 wt% DVB. Below 2 wt%, the
nished ion-exchange materials lack the
mechanical strength to resist the volume
changes, which occur under normal
operation. Above 16 wt%, the polymer
structure resists swelling, so that

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International Journal of Pharmaceutical Sciences and Research

production of a nished ion exchanger

becomes difficult and costly. The amount
of DVB determines the extent of swelling
and shrinking of ion-exchange resins. The
swelling would affect the rate of
hydration, the volume expansion of the
resin in a column, the rate of exchange of
ions, and the capacity of the resin to sorb
large molecules. Even after sorption,
some large molecules may be difficult to
elute unless the DVB fraction is quite low.
The excellent swelling properties of the
ion-exchange resins, such as potassium
salt of polymethacrylic acid resin
(Amberlite IRP-88), has been practically
used as a tablet disintegrating agent19, 20.
3. IONIZATION: In all ion exchangers, the
ionization of the attached functional
group is dependent on the Presence of
water in the matrix. The amount of water
that an ion-exchange resin will imbibe, in
turn, is dependent on the cross-linking of
the polymer. The ionization of the
functional group determines the type and
the strength of an ion exchanger. In
aqueous media, strong acid cation and
strong base anion-exchange resins are
fully hydrated; and the ions associated
with the functional group are always free
to exchange with ions of like charge in the
solution being processed. However, the
ionization in weak acid cation and weak
base anion exchangers is different. The
value at which ionization becomes
effective (pKa value) in resins containing
sulfonic, phosphoric or carboxylic acid
exchange groups is <1, 23, and 46,
respectively. Anion exchangers with
quaternary, tertiary, or secondary
ammonium groups have apparent pKa
values of >13, 7 9, and 5 9, respectively.
The pKa value of a resin will have a
signicant inuence on the drug release

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rate from the drugresinate in the gastric

uids18.
4. PARTICLE SIZE AND FORM: The rate of
ion exchange reaction depends on the size
of the resin particles. Decreasing the size
of the resin particles significantly
decreases the time required for the
reaction to reach equilibrium with the
surrounding medium; hence larger
particle size affords a slower release
pattern18.
5. POROSITY AND SWELLING: Porosity is
defined as the ratio of volume of the
material to its mass. The limiting size of
the ions, which can penetrate into a resin
matrix, depends strongly on the porosity.
The porosity depends upon the amount of
cross-linking
substance
used
in
polymerization method. The amount of
swelling is directly proportional to the
number of hydrophilic functional groups
attached to the polymer matrix and is
inversely proportional to the degree of
DVB cross linking present in the resin2.
6. STABILITY: The ion exchange resins are
inert substances at ordinary temperature
and excluding the more potent oxidizing
agents are resistant to decomposition
through chemical attack. These materials
are indestructible. They get degraded and
degenerated in presence of gamma rays2.
7. PURITY AND TOXICITY: It is necessary
to establish the safety/toxicity of the ionexchange resins because of very high
fraction of the resin in drugresin complex
(>60%). Most commercial products cannot
be used as such because they contain
impurities that cause severe toxicity
besides some pharmaceutical grade resins
(Amberlite
IRP
series
from

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International Journal of Pharmaceutical Sciences and Research

Rohm&Haas).Therefore,a
thorough
purication of the resin is required to
eliminate the impurities for the
pharmaceutical
application.
Puried
ionexchange resins are insoluble and
nontoxic. However, administration of
large enough quantities of ion-exchange
resin may disturb the ion strength in the
gastrointestinal uids and cause harmful
side effects21, 22.
8. SELECTIVITY OF RESIN FOR COUNTER
ION: Since ion exchange resin involves
electrostatic forces, selectivity mainly
depends on relative charge and ionic
radius of hydrated ions competing for an
exchange site and to some extent on
hydrophobicity of competitor ion2.
MARKETED RESINS USED AS TASTE
MASKING AGENT23, 24, 25, 26, 27: There are
various marketed resin used for taste
masking which are summarized with the
examples of bitter drugs in the table 2.
APPLICATIONS OF ION EXCHANGE RESIN
(IER)
IN
PHARMACEUTICAL
FORMULATIONS:
1. TASTE MASKING IN CHEWABLE
TABLETS AND CHEWING GUMS: Many
drugs taste very bitter, thus limiting their
use in chewable tablets. The ion-exchange
resin complex or drug-resinates offers a
method to eliminate the bitter taste and
not delay the onset of action. For
example, pseudoephedrine is tastemasked by
sorbing
it
into a
polymethacrylic acid ion-exchange resin
(Amberlite CG-50) in the chewable
Rondec decongestant tablet. Additional
taste masking was achieved by coating the
drug-resinate with a polymer mixture of

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4:1 ethyl cellulose and hydroxypropyl

methylcellulose28.
Nicorette is a widely used patented
product for smoking cessation. It contains
nicotine sorbed to a carboxylic acid ionexchange resin in a flavoured chewing
gum base. The drug-resinate offers a
slower drug release for absorption
through the buccal mucosa as the gum is
chewed. Nicotine is gradually available
over a 30- min period by the mechanical
chewing activity and the slow elution from
the resin particles. It was demonstrated
that the ion-exchange equilibrium was
rapid and incomplete due to the fixed
fluid volume surrounding the chewing
gum, but continuous chewing made fresh
solvent (saliva) available for the complete
release of the drug. A very fine particle
size was used in the chewing gum to avoid
grittiness of the ion-exchange resin29.
Other resins used for this purpose are
Indion-464, Tulsion-335, Amberlite IRP64,
Purolite C115HMR, Kyron-T-104 and
Kyron-T-114.
2. DRUG STABILIZATION: Complexing
active ingredients with ion exchange
resins prevent harmful interaction with
other components e.g. Vitamin B12 has
shelf-life of only a few months and
Vitamin B12 deteriorates on storage. This
necessitates addition of overages, leading
to significant increase in the cost of the
formulations. The stability of Vitamin B12
can be prolonged to >2 years by
complexing it with a weak acid cation
exchange resin (Indion- 264). This
complex is as effective as the free form of
the Vitamins23. Example of resins used for
this purpose are Indion-464, Tulsion-335,
amberlite IRP64, Purolite C100HMR.

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Table 2: Marketed Ion Exchange Resin as Taste Masking Agent; WEAK CATION EXCHANGERS
Product name
(Resin)

Matrix

Functional
group

Amberlite IRP64

Methacrylic

-coo

Amberlite IRP88

Methacrylic

-coo

Tulsion 335

Methacrylic

-coo

Tulsion 339

Methacrylic

-coo

Kyron-T-104

Methacrylic

-coo

Kyron-T-114

Methacrylic

-coo

Indion 204

Crosslinked polyacrylic

Indion 214

Crosslinked polyacrylic

Indion 234
Indion 294
Indion 464

Crosslinked polyacrylic
Crosslinked
polymethacrylic
Crosslinked
polymethacrylic

Standard
ionic form

Exchange
capacity

Examples of Drugs

10meq/kg

10meq/g

-coo

10meq/g

-coo

-coo

-coo

-coo

10meq/g

9.5meq/g

Spiramycin, ranitidine,
dextromethorphan,
Dimenhydrinate.
Talampicillin HCl, paroxetine,
beta-lactum antibiotics
Norfloxacin, ofloxacin,
roxithromycin
Chloroquine phosphate,
quinine sulphate,
ciprofloxacin, paracetamol
Cefuroxime Axetil,
Cefpodoxime Proxetil,
Norfloxacin
ItoprideHCl, Ofloxacin,
Tramadol HCl
Norfloxacin, ofloxacin,
Famotidine, roxithromycin,
dicyclomine HCl,
Azithromycin
Ciprofloxacin, chloroquine phosphate

Nicotine taste masking

Amodiaquine
HCl,Cetirizine Di HCl,
ChloroquinePhosphate Dicyclomine HCl
QuinineSulphate,Ibuprofen
Roxithromycin, Cefaclor
Metronidazol Benzoate,
Dextrometharphan,
Cloxacillin Sodium,
Erythromycin Estolate,
Ciprofloxacin HCl ,
Erdosteine , Azithromycin

Kyron-T-134

Crosslinked polyacrylic

-coo

Purolite C102DR

Methacrylic

-coo

Doshion P544

Methacrylic

-coo

cardio-tonics and anti-

depressants

Roxithromycin

STRONG CATION EXCHANGERS

Product name

Matrix

Amberlite IRP69

Styrene DVB

Tulsion 344
Kyron-T-154

Styrene DVB
Styrene DVB

Functional
group
-SO3H
-SO3H
-SO3H

Standard
ionicform
+
Na
Na

Na

Exchange
capacity
4.3 eq/kg
-

Examples of Drugs
ranitidine
Dextromethorphan,
dicyclomine HCl
Erythromycin Stearate

STRONG ANION EXCHANGERS

Product name

Matrix

Functional
group

Standard ionic
form

Indion 454

Crosslinked
polystyrine

-N R3

Cl

Exchange
capacity

Examples of Drugs

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3. CONTROLLED RELEASE DOSAGE

FORMS: A drug- resinate incorporated in a
tablet or capsule form has long been
considered as one of the methods for
controlled release applications. For
example, Biphetamine has been used for
several decades as an anti-obesity agent
and for behavior control in children. The
product contains amphetamine and
dextroamphetamine (1:1) sorbed to a
sulphonic acid cation exchange in a
capsule form, and is administered as once
or twice daily30. Adderal also contains the
same active drug.

The Pennkinetic system developed by the

Pennwalt Corporation is the most notable
application of the ion-exchange resins for
the preparation of controlled release
liquid suspensions33. In this system, the
drug-resinates are further treated with an
impregnating agent, for example, PEG
4000, to retard the rate of swelling in the
water and subsequently are coated with
ethylcellulose film, to act as a ratecontrolling barrier to regulate the release
of the drug from the system. The
advantages of this type of gastrointestinal
drug delivery systems are as follows;

4. CONTROLLED RELEASE ORAL LIQUID

SUSPENSIONS: Ion-exchange resin as drug
delivery carrier used mostly in controlled
release liquid preparations. Liquid
suspensions containing microparticles or
pellets offer many advantages for
pediatric and geriatric patients. However,
liquid dispersion systems often have
physical and chemical stability problems,
such as the leaching of the drug from the
microparticles into the suspending vehicle
and potential interactions of the carrier or
coating material with the vehicle during
storage31. The drug-resinate approach
offers a unique and advantageous way to
prevent the drug leakage during storage in
the liquid form32. In a liquid container, the
ion-exchange resins can maintain the drug
bound by keeping the liquid free of the
resin's counter-ions. When administered
orally, the ions in the gastrointestinal tract
will activate drug release from the drugresinate at a gradual rate. A ratecontrolling coating can often be applied
onto the drug-resinates to achieve the
desired release profile if the drugresinates does not achieve the desired
controlled release profile.

1. The rate of the drug release is

relatively constant and is not
dependant on pH condition, enzyme
activities, and temperature of the GI
tract.
2. The system is administered in the form
of large number of particles, which
helps to eliminate the release
differences due to changes in
gastrointestinal motility and gastric
emptying, because the dose will be
more evenly distributed in the GI tract.
3. It can be prepared in liquid suspension
form and can eliminate the bitter taste
of the drug.
Several commercially available controlled
release liquid suspensions using ionexchange resins are discussed below;
Delsym (Dextromethorphan): Delsym is
a liquid suspension product, designed to
provide relief of coughs as twice-a-day
dosage form in a flavored liquid form. The
active drug is bound to a sulphonic acid
ion-exchange resin and then the drugresinates are coated with ethylcellulose.
The bioavailability of the product is

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International Journal of Pharmaceutical Sciences and Research

equivalent to the dextromethorphan HBr

solution34.
Liquifer (Iron): Liquifer is an iron
controlled release suspension product,
designed to provide supplemental iron as
a once-a-day dosage form in a pleasanttasting liquid form35.The iron in the
ferrous state was bound to a sulphonic
acid ion-exchange resin. The rationale for
developing this product is to prevent high
concentrations of iron in the stomach,
which may cause gastrointestinal distress.
The iron-resin complex serves perfectly
for this purpose because no more than
25% of the iron in the iron-resin complex
would be solubilized in the stomach with
normal gastric fluid levels, thus allows
reduced gastrointestinal irritation. In
addition iron in resinate form improves
taste, reduces tooth staining, and
minimizes
possible
overdoses
as
compared to conventional products.
Penntuss
(Codeine
and

Chlorpheniramine): Penntuss is a liquid

suspension product designed for 12h
cough/cold relief. Two drugs are bound to
a sulphonic acid cation-exchange resin,
and the codeine resinates are coated with
ethylcellulose
while
the
Chlorpheniramine-resinates are uncoated
due to much high affinity for the resin36.
5. OPTHALMIC SUSPENSION: Betoptic S
is the sterile ophthalmic suspension
containing 0.25% betaxolol HCL, a
cardioselective beta-adrenergic receptor
blocking agent, in a resin suspension
formulation. This is the first drug-resinate
ocular product approved by the FDA and
is marketed in U.S. since February 199037.
It was designed to lower elevated
intraocular pressure. Alcon Laboratories
main purpose of developing this product

ISSN: 0975-8232

is to improve the ocular comfort of

betaxolol solution upon instillation
without compromising the efficacy. The
enhanced comfort of Betoptic S is based
on drug-resin complex in which the
positively charged drug is bound to a
cation exchange resin (Amberlite IRP 69).
Since Betaxolol HCL and the resin are
present in Betoptic S in approximately
equimolar ratio, conditions in the
suspension allow about 85% of the drug
to be bound to the cation-exchange resin
beads. In order to obtain ultra fine
ophthalmic quality suspension, the ionexchange resin beads are milled to a
mean diameter of 5m, which is smaller in
size to steroid particles found in
opthalamic formulations.
In the eye, the drug is released
from the drug-resinate by exchanging
with sodium ions in tears. Thus the drug is
released relatively slow in the tear. Since
betaxolol is released into the tear more
slowly from
Betoptic S than from
Betoptic solution, ocular comfort is
enhanced. In addition, carbomer 934P, a
water soluble polyacrylic acid polymer is
added to stabilize the suspension and
increase the ocular residence time.
Bioavailability studies showed that 0.25%
resinate suspension was equivalent to
0.5% Betoptic solution.
Also in two U.S. patents, Chang
teaches the use of pH sensitive and
thermo-sensitive gelling agents to slow
down the drug release and to stabilize the
suspension.
The
preparations
are
particularly suitable for ocular delivering
of drugs (e.g., epinephrine, levobunolol) 38,
39
.

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International Journal of Pharmaceutical Sciences and Research

ISSN: 0975-8232

6. TABLET DISINTEGRATION [IMPROVED

TABLET DISINTEGRATION PROPERTIES]:
Many tablets disintegrant owe their
action to capacity to absorb water and
swell up. Fine particle size ion exchange
resins have shown superiority as
disintegrating agent due to their
considerable swelling pressure upon
hydration. Advantages of ion exchange
resins over conventional disintegrating
agents are;

availability. It was questionable, however,

if any significant delay in Absorption
would occur. While assaying amine drugs
buffers above 7 or below 3 or Solutions
with high cation concentration may be
used to affect complete drug elution42.

1. Rate of permeation of water and

subsequent swelling is very fast and cut
down the disintegration time.
2. Ion exchange resins do not have
adhesive tendency on hydration; hence
tablet disintegrates evenly without
formation of lumps.
3. Ion exchange resin is effective in low
concentration as disintegrants.
4. Ion exchange resin incorporation
confirms greater hardness to tablet.
5. Ion exchange resin work equally
efficiently with hydrophilic as well as
hydrophobic
formulations,
especially with the later where the
conventional
disintegrants
are
ineffective.

7.
BIOADHESIVE
SYSTEM
FOR
TREATMENT OF GASTRIC MUCOSA: Ion
exchange resin may have inherent
bioadhesive properties similar to those of
highly charged polyanions43. Hence ion
exchange resins may be useful in
mucoadhesive systems for topical
treatment of stomach such as H. pylori
infection for prolonging the gastric
residence of amoxicillin and cimetidine44.

Because of their unusually large

swelling
capacities
polymethacryllic
carboxylic Acid ion exchange resins have
found usage in pharmacy as tablet
disintegrants; for example pollacrilline a
potassium salt of weakly acidic cation
exchange resin with methacrylic acid
divinyl benzene matrix40, 41.
Borodkin and Yunker investigated
chances of interference of cation
exchanger disintegrants with drug
availability and assay. They concluded that
such agents should not affect total in vivo

Examples of resins used for this purpose

are Indion-234S, Tulsion-339, Amberlite
IRP88,
Kyron-T-314,
and
Purolite
C115KMR

8. CHOLESTEROL REDUCER: Cholesterol is

essential for human and animal life, but
an excess of cholesterol in the blood is
one of the most important and recognized
risk factors in cardio-vascular disease.
Cholesterol is converted by the liver into
bile acids, which, when discharged into
the Duodenum, emulsify ingested fats,
thereby assisting digestion. The bile acids
are absorbed through the intestine and
are returned to the liver, where they are
converted, through a chain of reactions,
to low density lipoprotein (LDL)
cholesterol.
The metabolism of cholesterol is
subject to a delicate balance. This balance
can be disrupted to the point where there
is such a high accumulation of LDL
cholesterol in the blood that it
precipitates as cholesteryl esters on the
walls of blood vessels, restricting flow and

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International Journal of Pharmaceutical Sciences and Research

ISSN: 0975-8232

leading to potential heart attacks. It can,

therefore, be advantageous, in such cases,
to
reduce
cholesterol
levels.
Cholestyramine is a non-absorbable, nonmetabolisable anion exchange resin
which, by complexing the bile acids,
prevents their re-absorption and allows
them to pass through the body. The
reduction of bile acids causes a depletion
of hepatic cholesterol, which, in turn,
stimulates the transformation of LDL
cholesterol into hepatic cholesterol,
thereby reducing LDL cholesterol levels
and lowering the total cholesterol level in
the blood27.

than the dissolution rate of the pure

drug44.

The advantage of Cholestyramine

over other drugs is that there are little
side effects. Besides the treatment of
hypercholesterolemia,
Cholestyramine
has other medical Applications, such as:
improving
diarrhoeal
states
by
significantly reducing the activity of
endotoxins; treating vitamin D3 overdose;
and as recent studies indicate, regression
in
arteriosclerosis.
Listed
in
pharmacopoeia as Cholestyramine,
Purolite A430MR is a powdered Anion
exchange resin in the chloride form. The
powder resin is flavored by the
Pharmaceutical Company, and prepared
in doses to be dispersed in water or fruit
juice for oral consumption. Examples of
resins used for this purpose are Indion454,
Tulsion-412(CHL),
Duolite
AP143/1093, and Purolite A430MR.

1. Each individual molecule is bound to a

functional site-there is no crystal lattice
energy to overcome.

9. IMPROVED DISSOLUTION OF POORLY

SOLUBLE DRUGS: The slow dissolution of
poorly soluble drugs is well known
problem
responsible
for
poor
bioavailability. The release rate of such
drugs from resinates can be much quicker

Eg. Indomethacin which is soluble up to ca

6ppm in simulated gastric fluid, but is
release very quickly from resinate. the
commercially
available
product
indomethacin uses micronization of the
drug
powder
to
achieve
rapid
dissolution44.Not all poorly soluble drugs
are amenable to micronization because of
the problems including low melting point,
dust formation and agglomeration.ion
exchange
resins
are
convenient
alternative. The rapid dissolution occurs
due to two factors,

2. The ion exchange

relatively hydrophilic
water and aqueous
access in to the
structure- eliminating
wetting-out' the drug.

materials are
and so allow
solutions easy
3-dimensional
problems with

However this technique like micronization

increases the rate of dissolution. It does
not increase the solubility of the drug.
10. ANTI-DELIQUESCENCE: Deliquescence
is the property of a solid whereby it
absorbs so much water that it dissolves in
the water it absorbs. This problem is very
difficult to solve, and requires the use of
specialized equipments or careful
scheduling of a production in dry
seasons44. A very recent discovery by
Rohm and Hass research laboratories
show that using resinates can eliminate
deliquescence during manufacturing and
storage. Rohm and Hass have filed the

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International Journal of Pharmaceutical Sciences and Research

patent application for it. They have found

that resonates of deliquescent and highly
hygroscopic drug retain the properties of
the resin and are not deliquescent and
remain free flowing powders. Their water
absorption characteristics are similar to
those of unloaded resin.so, that any
formulation equipment that can handle
the resin can handle the resinate of the
deliquescent drug without need for
special manufacturing conditions.
For example sodium valproate is a drug
which is well known to be highly
deliquescent. However they have found
that valproate resinates remain freeflowing even after exposure to ambient
air.
11.
POLYMORPHISM:
Unlike
deliquescence, polymorphism is a very
common problem in 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 problems
can result in significant stability problems
for the final dosage form44. Ion exchange
resin presents a unique way to deal with
the problem. a drug resinate is an
amorphous solid that cannot crystallize or
even form hydrates. In addition the
release of the drug from the resinate is
independent of the crystal form that was
used to make it. Consequently using
resinates completely eliminate any
problem with polymorphism.
12. TREATMENT OF HYPERKALEMIA:
Excess potassium in the blood is a
common condition in chronic renal failure
and is potentially life threatening. The
action of the resin is simple ion exchange
.the resin is in sodium or calcium form and
this ions are exchanged with the excess

ISSN: 0975-8232

potassium in the blood stream as the resin

pass through the GI tract. Typical dosage
amounts are 15-60 g per day for extended
period of time. Formulations are either
powder sachet or aqueous suspensions23.
Various resin used for this purpose are
Indion-404, Tulsion-344, Tulsion-345,
Purolite C100NaMR, Purolite C100CaMR.
13. SITE-SPECIFIC DELIVERY OF DRUGS
FOR CANCER TREATMENT: Entrapment of
anticancer drugs within the particulate
carriers (microspheres, microcapsules) is a
popular approach for the development of
delivery systems for cancer treatment.
Several anticancer drugs (e.g. doxorubicin)
are ionic in nature and can be complexed
with IER. Attempts have been made to
deliver some of these drugs in a
controlled-release
fashion
to
the
45, 46
anticancer cells with the help of IER
.
These studies revealed that the drug
loading is at its maximum level with the
IER complex approach. The mechanism of
complexation of doxorubicin with ionexchange albumin microcapsules was
studied11. These studies proved the
chemical Stability of anticancer drugs in
IER microcapsules.
CONCLUSION: Taste masking of drug by
ion exchange resin is economical, simple
and
convenient
method.
Various
techniques are used to mask the bitter
taste of drug. But one of the most
Economical method for taste masking is
the use of ion exchange resin. Ion
exchange resins have been used in
pharmacy and medicine for various
functions,
which
include
tablet
disintegration,
bioadhesive
systems,
sustained release systems. The use of IER
in drug delivery research is gaining

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International Journal of Pharmaceutical Sciences and Research

importance and commercial success. In

addition to oral drug delivery, IER systems
are being explored for site-specific,
transdermal, nasal and ophthalmic
Routes. Moreover, several novel concepts,
such as sigmoidal Release, floating, pH
and ionic strength-responsive systems,
have shown the potential use of IER in
drug delivery.
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