Current Drug Delivery, 2007, 4, 123-129 123

Microsponge Delivery System

Vikrant Chadawar and Jessy Shaji*

Dept. of Pharmaceutics, Prin. K.M.Kundnani College of Pharmacy, Plot No. 23, Jote Joy Building, Cuffe Parade,
Colaba, Mumbai- 400 005, India

Abstract: Microsponges are polymeric delivery systems consisting of porous microspheres having a size range in be-
tween 5 to 300 μm depending upon the degree of smoothness or after feel required for the end formulations. Microsponge
Delivery System MDS is a unique technology for controlled delivery of drug.
The present review introduces Microsponge technology along with its synthesis, characterization, programmable parame-
ters and release mechanism of MDS. Wide ranges of applications are also suggested to develop drug or cosmetic products
with enhanced safety and efficacy. MDS can provide increased efficacy for topically active agents with enhanced safety,
extended product stability and improved aesthetic properties in an efficient and novel manner.
Keywords: Microsponge, quasi emulsion diffusion solvent method, free radical suspension polymerization, porous micro-
sphere, release mechanism.

INTRODUCTION  To control the release of active agents which are ir-

The ability to control the delivery rate of active agents to
a predetermined site in the human body has been one of the
biggest challenges till date, met by continued innovations.
During this time, some areas of Pharmaceutical research
have been focused on controlled delivery of systemic drugs.
Several predictable and reliable systems were developed for
systemic drugs under the heading of “Transdermal delivery”
using skin as a portal of entry. The risk and hospitalization of
the patients under a close supervision associated with other
methods lead to the development of “Transdermal Therapeu-
tic Systems” for topical application, which could mimic in-
travenous infusion. This approach was first introduced by
Ciba-Geigy by successfully marketing Transderm-Scop
patch for 72hr as a prophylactic in the treatment of motion
sickness. Transdermal patches developed in the 1970 im-
proved the delivery of drugs resulting into better control of
therapeutic doses [1].
Controlled release of drugs onto the epidermis is with
assurance that the drug remains primarily localized and does
not enter the system in significant amounts. Although trans-
dermal delivery systems can be efficient in supplying drugs
for systemic effects, they are not practical for controlling the
delivery of materials whose final target is the skin itself. And
this is an area of research that has been recently addressed
[2, 3].
Thus there is need to develop novel topical programma-
ble delivery system for the following reasons:-
 Systems present either on the skin surface or within
the epidermis minimize its transdermal penetration
into the body.
*Address correspondence to this author at the Dept. of Pharmaceutics, Prin.
K.M.Kundnani College of Pharmacy, Plot No. 23, Jote Joy Building, Cuffe
Parade, Colaba, Mumbai- 400 005, Índia; Tel: +91 22 22164387: Fax: +91
22 22165282; E-mail: jshaji@rediffmail.com
ritating or allergic at high local concentration.
 Many topical agents e.g. Antibiotics, Steroids re-
quire epidermal localization of the drug without be-
ing absorbed into systemic compartment.
 Available topical vehicles such as Ointments often
prove aesthetically unappealing.
 These vehicles lacks patient compliance by provid-
ing the greasiness; stickiness or even a discoloration
in clothing’s making daily wear unpleasant.
 Most existing topical drug formulations have un-
controllable evaporation of the active ingredient,
unpleasant odour and the potential incompatibility
of one or more drugs with each other or with the
vehicles.
 The cosmetic applications of deodorants, Sun-
screens etc. requires controlled topical delivery of
the actives.
The MDS is a polymeric microsphere system uniquely
fulfilling these requirements by providing topical controlled
drug delivery systems [4].
Additionally various companies are utilizing its patented
Microsponge system in the development of oral drug deliv-
ery system for improved bioavailability. There are many
drugs that have a very low rate of solubility and whose effi-
cacy could substantially be improved if their rate of solubili-
sation and hence bioavailability could be increased. Such
systems are still in early research and developmental stage,
but a successfully done In-Vitro studies and preliminary In-
vivo studies indicate that a MDS enhance the rate of dissolu-
tion of poorly water soluble drugs by entrapping such drugs
in Microsponge pores. These pores are very small and the
drug is in effect reduced to microscopic particles and thus
significantly increases surface area by increasing the rate of
solubilisation. An added benefit is that the time taken by

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124 Current Drug Delivery, 2007, Vol. 4, No. 2
MDS to traverse the small intestine is significantly increased
thus maximizing the amount of drug that is absorbed. This
could provide much better treatment to number of diseases
including Ulcerative Colitis and Chronic Constipation. Also
in the development of modified MDS that are able to deliver
the drugs to the colon forming Microsponge colonic delivery
system.
Another approach of using MDS technology is in medi-
cal field by using Collagen Microsponge [5-8] which is
mainly used in bio-engineering [9] as well as tissue engi-
neering [10].
MICROSPONGE TECHNOLOGY
Microsponges are polymeric delivery systems consisting
of porous microspheres, these are tiny sponge like spherical
particles that consists of myriad of interconnecting voids
within a non-collapsible structure with large porous surface
[11]. The size of these Micropsonges can be varied, usually
from 5-300
m in diameter depending on the degree of
Smoothness, or after feel required for the end formulation. A
typical Microsponge bead is a 25
m sized sphere which can
have upto 250,000 pores and an average internal pore struc-
ture equivalent to 10 feet in length with average pore volume
of about 1ml/gm. The surface can be varied from 20-500
m2/gm and pore volume range from 0.1-0.3 cc/gm [12].
Fig. (1). A typical diagram of Microsponge.
The scanning electron microscopy of the ruptured bead
reveals it’s internal structure as a “Bag of Marbles”, The
porosity is due to the interstitial spaces between the “Mar-
bles.” These porous microspheres can entrap a wide range of
active ingredients such as emollients, fragrances, essential
oils, sunscreens, anti-infective and anti-inflammatory agents.
These entrapped active agents can be incorporated into many
product forms, such as creams, lotions, powders and soaps.
After the product is applied, the entrapped material are then
delivered to the skin in a controlled time release pattern or a
preprogrammed manner through the use of several different
‘triggers’, rubbing or pressing the Microsponge after it has
Chadawar and Shaji
been applied to the skin, elevates skin surface temperature
introducing solvents for the entrapped materials such as wa-
ter, alcohol or even perspiration and controlling the rate of
evaporation. Active ingredients entrapped in the porous po-
lymeric structure display altered behavior, with respect to
their release, which is restricted and prolonged.
MICROSPONGE SYNTHESIS
Microsponge particles are conveniently synthesized
mainly by two methods namely,
1. Quasi Emulsion Solvent Diffusion method
2. Free Radical Suspension Polymerization
The brief discussions of these methods is as follows,
1. Quasi Emulsion Solvent Diffusion Method
All Microsponges were prepared by quasi-emulsion sol-
vent diffusion method uses an external phase and internal
phase. The external phase mostly consists of distilled water
and PVA [13] while organic internal phase consists of drug,
ethyl alcohol, polymer and Triethyl citrate (TEC)/ Tri-
chloromethane [14] which was added at an amount of 20%
of the polymer in order to facilitate the plasticity [15]. At
first, the internal phase was prepared at 600C and added to
the external phase at R.T. After emulsification, the mixture
was continuously stirred for 2 hours. Then the mixture was
filtered to separate the microsponges and the prepared prod-
uct was washed and dried by vacuum oven at 400C for 24
hours.
2. Free Radical Suspension Polymerization
Microsponges were conveniently prepared by free radical
suspension polymerization in a emulsified liquid-liquid sys-
tem [16-18]. Particles forming polymerization mixtures are
usually two phase systems. The monomers are referred to as
‘monomer phase’ or ‘dispersed Phase’; the immiscible liquid
phase containing the dispensed (or dissolved) monomer is
defined as “Polymerization medium.”
In addition to the monomers and polymerization medium,
another liquid (miscible with the monomer and immiscible
with the medium) may also be added to the monomer to
form a pore network. This liquid is known as ‘monomer di-
luent’ or ‘porogen’ and belongs to the category of inert, non
polar organic solvents when added to the polymerization
reaction, polymeric beads with open, porous structures can
be obtained and they look just like sponges under SEM,
hence the name ‘MICROSPONGES’ [19].
For preparing Microsponge, the requirements are mono-
mer namely Styrene, PHEMA, Crosslinking Agents is Divi-
nyl Benzene and Porogen is Toluene [20].
It is important to maintain the temperature for most effi-
cient operation. Temperature of the reaction mix dictates the
rate of decomposition, the initiation into free radicals and
hence affecting the rate of polymerization.
Once the suspension is established with discrete droplets
of the desired size, polymerization is affected by activating
the monomers either by catalysis, increased temperature or
irradiation.
Microsponge Delivery System
The result is a series of polymer ladders wrapping around
one another into solid Micropsheres. As the Polymerization
process continues, a spherical structure is produced contain-
ing thousands of Micropsheres buched together like grapes,
forming interconnecting reservoirs in which the porogen is
entrapped. These reservoirs open onto the surface of the
spheres through which active ingredient can be released
when triggered.
Once polymerization is complete the solid particles that
result from the process are recovered from the suspension.
The particles are then washed and processed until they are
substantially ready for use. Particle formation and incorpora-
tion of the functional substance is thus performed as a single
step. This may be termed as one step process.
SUSPENSION POLYMERIZATION- SYSTEM SET UP
[19-25]
Polymerization is carried out in a three necked flask
heated by a heating mantle or on a water bath. It is important
to make certain that the system is assembled correctly and is
operating properly before proceeding further; once stirrer is
started it may become difficult to make any adjustment.
Fig. (2). Microsponge Synthesis.
Current Drug Delivery, 2007, Vol. 4, No. 2 125
The schematic representation of the system employed for
suspension polymerization is shown in Fig. (2).
Fig. (2) shows a cylindrical reactor vessel with symmet-
rically matching stirring arrangement designed [18].
For large scale Suspension Polymerization, the reactor
has spiral stirring arrangement that provides a relatively tur-
bulence free and uniform distribution of the mixing force
throughout the Suspension mixtures. This in turn leads to the
formation of relatively stable suspension system, and reduces
the chance of inadvertent particle coagulation and experi-
mental failure.
ENTRAPMENT OF FUNCTIONAL SUBSTANCE
The active ingredients can be incorporated into the Mi-
crosponge mainly by two conventional methods:
One step process where incorporation of active agent and
particle formation is carried out in a single step. The active
agent in this case usually is a porogen.
Placement of the functional substance inside the reservoir
may be achieved by impregnation of the performed dry po-
rous polymer particles according to techniques, such as con-
tact absorption.
126 Current Drug Delivery, 2007, Vol. 4, No. 2
PROGRAMMABLE PARAMETERS [4]
The primary physical parameters of Micropsonges are
Particle size, Pore structure, and parameters like diameter,
volume and release characteristics. Each can be predesigned
at the time of manufacture by altering the components and
polymerization conditions required to produce a mi-
crosponge.
1. Particle Size
The free flowing characteristics of the powders can be
created by tightly controlling the diameter of the micro-
spheres at the time of polymerization. The diameters of 5-
300
m are feasible. Smaller particle feels like talcum even if
they contain only 50% mineral oil. Larger particle size may
be obtained if desired. Particle size thus may have some in-
fluence of the release rate of the active ingredient from the
Microsponge. The smaller the particle size, the slower the
release rate.
2. Pore Diameter and Volume
Pore volume (Void volume) determines the amount of
active substance that can be incorporated in the Microsponge
system. Both pore volume and diameter are vital in control-
ling the intensity and duration of effectiveness of the active
ingredient. Pore diameter also affects the migration of the
active ingredient from the Microsponge into the vehicle in
which the material is dispersed. As a result, the diameter of
the pores can have direct impact on the stability of the final
formulations.
3. Resiliency
The degree of crosslinking during the polymerization to
obtain softer or harder beads according to the need of the
product can be controlled. A 10% crosslinking is enough to
retain the strength and shape after removal of active agent
from pore network. Increase in the crosslinking slows down
the release rate.
Table 1. Comparison of Microsponge with Microencapsulation Technology [26]
Microsponge Delivery System
Concept Sponge
Shell Pores
Release Mechanism Depend upon,
1. Pressure
2. Volatility
3. Temperature
4. Solvent
5. Partition Coefficient
Amount Released It depends on different programmable parameters
such as,
1. Particle Size
2. Pore volume and Size
3. Resiliency
Chadawar and Shaji
4. Monomer Composition
Selection of the monomer depends upon the active ingre-
dient and vehicle into which it is dispersed, and the hydro-
philicity or lipophilicity may be manipulated to provide con-
trol on release of materials such as lipids, humectants, sun-
screens, vitamins, fragrances etc.
RELEASE MECHANISM
The aforementioned programmable parameters can be
effectively manipulated to design Microsponge delivery sys-
tem for the release of functional substance over a period of
time in response to one or more external stimuli. The release
mechanism of this system is mainly:-
a. Sustained or Time Release
In the development of a sustained release Microsponge,
different physical and chemical parameters of the entrapped
active substance such as volatility, viscosity and solubility
will be studied while in case of polymeric Microsponge pore
diameter, volume, and resiliency of the polymeric Mi-
crosponge are evaluated to give necessary Sustained release
effects.
b. Release on Command
Microsponges can be designed to release the given
amounts of active ingredients over time in response to one or
more external triggers.
1. Pressure Release
Microsponge system releases fluid when pressed or
squeezed, thereby replenishing the level of entrapped active
ingredient onto the skin. The amount released may also de-
pend upon the release of the sponge and the resiliency of the
Microsponges. In comparison to Microcapsules containing
mineral oil for emmoliency studies with the help of Gas
bearing electrodynamometer [27] the Microsponge shows
much more softening effect than that of Microcapsules.
When the subjects were rubbed on the applicated area for 3
Microencapsulation
Capsule
Complete
Rupture of Cells
100%
Microsponge Delivery System
Table 2. Comparison of Microsponge with Liposome Technology [26]
Microsponge Delivery System
Concept Sponge
Stability Totally stable over a broad
range of pH, temperature,
vehicle and ingredients.
Microbiological Stability Preservatives are not required
Programmable Characters Chemical Composition,
Particle size, Resiliency,
Pore volume and diameter.
Entrapment efficiency 50-60%
Cost Cost Effective
Quality Control Simple: Easily available
Raw materials of adequate purity.
hours post-application of formulations, Microsponge deliv-
ery system gave a larger increase in the release. The duration
of emmoliency were also greatly extended for the Mi-
crosponge systems. It was found that greater softening effect
was observed in Microsponge delivery system than that of
Microcapsules during 6 hours study.
Corticoids produce a local blanching effect on the skin
caused by vasoconstriction[28].
In-vivo study of the fluocinolone acetonite was applied to
the forearm of the test subjects where blanching effect was
studied after application of the formulation. Observation
indicates that sustained release was effective up to 32 hrs.
2. Temperature Release
The release of active Ingredients from microsponges can
be triggered by temperature. Some of the entrapped materials
such as sunscreens and emollients can be too viscous at room
temperature to diffuse spontaneously from the Microsponge
on to the skin. When warmed by the skin temperature, the
Sun or other heat source, their viscosity may decrease, re-
sulting in increased flow rate.
A microsponge formulation containing 50% of Octyl
dimethyl PABA (sun protective) was evaluated for release
profiles at 37oC and at room temperature by gravimetric
analysis. The microsponges were incorporated into oil in
water emulsion at 2.8% level to provide 1.4% sunscreen
concentration [29]. Then this preparation was kept in an
oven at 37oC and at room temperature. After 4 days, the
room temperature sample was placed into the oven along
with other sample, it was found that the release was in-
creased when placed at higher temperature than at room
temperature.
3. pH
The pH responsive MDS involves coating of Conven-
tional Microsponge delivery systems with enteric-coating
type of material, which imparts pH responsiveness to this
delivery system. The studies were performed by using highly
Current Drug Delivery, 2007, Vol. 4, No. 2 127
Liposomes
Lipid bilayers
Potential Problems
Preservatives are required
Chemical Composition,
Particle Size.
Approx. 30%
Expensive
Complex: Requires Ultra Pure raw materials.
water-soluble dye. The pH response studies were carried out
in USP spindal dissolution apparatus. At acidic pH of around
3 there was no remarkable release but when the pH was in-
creased to 8 the release of up to 80% was obtained. So it was
found that at lower pH the release was less but by increasing
the pH the release rate was increased. So the rate of drug
release is to be modulated as per the requirements.
4. Solubility
The change in polarity of the external medium e.g. water
or perspiration, may trigger the release rate of active ingredi-
ents from MDS. For e.g. Dry microsponge loaded with wa-
ter-soluble ingredients, such as antiperspirants or antiseptics,
release ingredients in the presence of water. Release can also
be activated by diffusion, taking into considerations the par-
tition coefficient of the ingredients between the Microsponge
and the outside system. This type of Microsponge delivery
system can be loaded to a high payload levels but the release
of active will not occur until Microsponges was placed into a
swelling medium. Microsponge containing D&C red dye
was kept in ethanol, no perceptible amount of dye was no-
ticed even though the dye is soluble in ethanol because of
inability of ethanol to swell Microsponge delivery systems.
But when external medium was replaced with water, the re-
lease was triggered due to change in swelling of MDS, thus
the release rate and solubility parameter values were corre-
lated.
SAFETY PARAMETERS
As such Microsponge delivery systems are made up of
biologically inert polymers, the substantiation of safety-
required insight of more than the 30 safety parameters such
as skin irritation [30,31] (in rabbits and humans), eye irrita-
tion (in rabbits), oral toxicity (in rats), mutagenicity (in bac-
teria), and allerginicity (in guinea pigs) demonstrate that the
polymers are non irritating, non mutagenic, non allergenic,
non toxic and non biodegradable. Furthermore, preliminary
data indicates that upon injection into the skin, some Mi-
crosponge systems are not recognized as foreign bodies and
cause no reactions in the body in response to their presence.
128 Current Drug Delivery, 2007, Vol. 4, No. 2 Chadawar and Shaji

Table 3. Potential Areas of Applications for Microsponge POSSIBLE AREAS FOR MICROSPONGE DELIVERY
Delivery System SYSTEM
These externally modulated topical controlled drug de-
Activities Advantages livery systems offer a range of advantages to a formulator by
enhancing its safety and efficacy of the product. Drugs ex-
Antiacne Enhanced Efficacy plored in MDS are mainly Ketoprofen, Benzoyl peroxide,
With decreased irritancy and Sensitization (e.g. Retinol, Fluconozole, Ibuprofen, Tretinoin, 5- Flurouracil,
Benzoyl Peroxide) Trolamine [39,40].
Anti- Reduced skin allergy and dermatoses The recent data demonstrate that the MDS have also po-
inflammatory Long lasting activity can be achieved (e.g. Hydro- tential in the wide range of applications including pain man-
cortisone) agement, osteoarthritis, anti-adhesion, anti-inflammatory,
anti-infective, ophthalmic diseases, bone growth, restonesis,
Antidandruff Reduced unpleasant odor and Irritancy (e.g. Zinc and tissue engineering. Researcher found that the initial tox-
Pyrithione) icity data is safe for use in the body. Furthermore, MDS have
With enhanced safety and efficacy controlled drug-release rates, both short term and long term.
Antipruritics Enhanced activity for anti-itching compounds
Efficacy improved against pruritics CONCLUSION
Antifungals Provides sustain release activity With demand for innovative and highly efficient Pharma-
All day relief from fungal problems ceutical as well as Cosmetic products, the market holds con-
siderable potential for Microsponge technology and the ver-
Sunscreens Reduced irritancy and sensitization satility they offer. As formulators consider new and creative
Increase protection against sun burn and sun related ways to deliver actives, they can realize the full capabilities
problems of these unique materials providing enhanced safety, im-
(Aging and skin irritancy) proved stability, reduced side effects from actives, enhanced
Skin depigmen- Stabilization and protection of skin bleaches against
multifunctionality and improved ingredient compatibility.
tation oxidation
Complemented by novel development approaches and crea-
Improved efficacy and aesthetic appeal of the
tive formulation techniques, Microsponge delivery system
product
can be a winning strategy for a new generation of Pharma-
(e.g. Hydroquinone)
ceutical and Cosmetic industry.

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Received: September 20, 2006 Revised: December 04, 2006 Accepted: December 14, 2006