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International Journal of Biopharmaceutics
Journal homepage: www.ijbonline.com
IJB
A REVIEW: MICROSPONGE DRUG DELIVERY SYSTEM
Poornima Pandey* ,Vikas Jain and SC Mahajan
Mahakal Institute of Pharmaceutical Studies, Ujjain (M.P) 456001 India.
ABSTRACT
Microsponges are porous, polymeric microspheres that are mostly used for prolonged topical administration.
Microsponges are designed to deliver a pharmaceutically active ingredient efficiently at minimum dose and also to enhance
stability, reduce side effects, and modify drug release profiles. Microsponges are prepared by several methods utilizing
emulsion system or by suspension polymerization in a liquid–liquid system. The most common emulsion system used is oilin-water (o/w), with the microsponges being produced by the emulsion solvent diffusion (ESD) method. It was shown that
the drug: polymer ratio, stirring rate, volume of dispersed phase influenced the particle size and drug release behaviour of
the formed microsponges and that the presence of emulsifier was essential for microsponge formation Lornoxicam is a new
nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic
properties. Lornoxicam differs from other oxicam compounds in its potent inhibition of prostaglandin biosynthesis, a
property that explains the particularly pronounced efficacy of the drug. In present investigation the formulation of
microsponge loaded controlled release percutaneous gel of Lornoxicam with different concentration of Eudragit RX100, and
ethyle celulose were used to study anti-inflammatory and antipyretic activity for long duration.
Key words: Microsponge, Gel, Anti-inflammatory, Controlled release and Topical drug delivery.
INTRODUCTION
A Microsponge drug delivery system (MDDS)
is a patented, highly cross-linked, porous, polymeric
microspheres polymeric system (10-25 µ) consisting of
porous microspheres particles consisting of a myriad of
inter connecting voids within non-collapsible structures
with a large porous surface that can entrap wide range of
actives (cosmetics, over-the-counter (OTC) skin care,
sunscreens and prescription products) and then release
them onto the skin over a time and in response to
trigger. A typical 25µm sphere can have up to 250000
pores and an internal pore structure equivalent to 10ft in
length providing a total pore volume of about 1ml/g.
Microsponge do not pass through the skin (capable of
holding four times their weight in skin secretions).
Corresponding Author
Poornima Pandey
E-mail: [email protected]
Rather, they collect in the tiny nooks and
crannies of skin and slowly release the entrapped drug, as
the skin needs it. The microsponge system can prevent
excessive accumulation of ingredients within the
epidermis and the dermis. These products are typically
presented to the consumer in conventional forms like
creams, gels or lotions and they contain relatively high
concentration of active ingredients. Microsponges are
polymeric delivery systems consisting of porous
microspheres that can entrap a wide range of active
ingredients such as emollients, fragrances, essential oils,
sunscreens, and anti-infective, anti-fungal, and antiinflammatory agents.
The MDS has advantages over other
technologies like microencapsulation and liposomes.
Microcapsules cannot usually control the release rate of
actives. Once the wall is ruptured the actives contained
within microcapsules will be released. Liposome suffer
from lower payload, difficult formulation, limited
chemical stability and microbial instability.
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HISTORY OF MICROSPONGE
The microsponge technology was developed by
Won in 1987 and the original patents were assigned to
Advanced Polymer Systems, Inc. This Company
developed a large number of variations of the technique
and applied those to cosmetic as well as OTC and
prescription pharmaceutical products. At the present
time, this interesting technology has been licensed to
Cardinal Health, Inc. for use in topical products.
HYPOTHETICAL MECHANISM OF MICRO
SPONGE
The active ingredient is added to the vehicle in
an entrapped form. As the microsponge particles have an
open structure (i.e., they do not have a continuous
membrane surrounding them), the active is free to move
in and out from the particles and into the vehicle until
equilibrium is reached, when the vehicle becomes
saturated. Once the finished product is applied to the
skin, the active that is already in the vehicle will be
absorbed into the skin, depleting the vehicle, which will
become
unsaturated,
therefore,
disturbing
the
equilibrium. This will start a flow of the active from the
microsponge particle into the vehicle, and from it to the
skin, until the vehicle is either dried or absorbed. Even
after that the microsponge particles retained on the
surface of the stratum corneum will continue to gradually
release the active to the skin, providing prolonged release
over time. This proposed mechanism of action highlights
the importance of formulating vehicles for use with
microsponge entrapments. If the active is too soluble in
the desired vehicle during compounding of the finished
products, the products will not provide the desired
benefits of gradual release. Instead they will behave as if
the active was added to the vehicle in a free form.
Therefore, while formulating microsponge entrapments,
it is important to design a vehicle that has minimal
solubilizing power for the actives. This principle is
contrary to the conventional formulation principles
usually applied to topical products. For these
conventional systems it is normally recommended to
maximize the solubility of the active in the vehicle. When
using microsponge entrapments, some solubility of the
active in the vehicle is acceptable, because the vehicle
can provide the initial loading dose of the active until
release from the microsponge is activated by the shift in
equilibrium from the polymer into the carrier. Another
way to avoid undesirable premature leaching of the active
from the microsponge polymer is to formulate the
product with some free and some entrapped active, so the
vehicle is pre-saturated. In this case there will not be any
leaching of the active from the polymer during
compounding. The rate of active release will ultimately
depend not only on the partition coefficient of the active
ingredient between the polymer and the vehicle (or the
skin), but also on some of the parameters that
characterize the beads. Examples of these include surface
area and primarily, mean pore diameter. Release can also
be controlled through diffusion or other triggers such as
moisture, pH, friction or temperature.
Potential Advantages of the Microsponge Drug
Delivery System
• Microcapsules cannot usually control the release rate
of the active pharmaceutical ingredients (API). Once the
wall is ruptured the API contained within the
microcapsules will be released. Can the MDS can do it, is
the question.
• Liposomes suffer from a lower pay load, difficult
formulation, limited chemical stability, and microbial
instability. Do the MDS have a wide range of chemical
stability and are they easy to formulate?
• MDS have stability over a pH range of 1 - 11.
• Stable up to temperature 130 o C.
• Pay load is up to 50 - 60%.
• Free flowing and cost effective.
• Microsponges are microscopic spheres capable of
absorbing skin secretions, therefore, reducing oiliness
and shine from the skin.
• Microsponge formulations are self sterilizing as their
average pore size is 0.25μm where bacteria cannot
penetrate.
CHARACTERISTICS OF MATERIALS THAT IS
ENTRAPPED IN MICROSPONGES
Most liquid or soluble ingredients can be
entrapped in the particles. Actives that can be entrapped
in microsponges must meet following requirements,
• It should be either fully miscible in monomer or
capable of being made miscible by addition of small
amount of a water immiscible solvent.
• It should be water immiscible or at most only
slightly soluble.
• It should be inert to monomers.
• The solubility of actives in the vehicle must be
limited to avoid cosmetic problems; not more than 10 to
12% w/w microsponges must be incorporated into the
vehicle. Otherwise the vehicle will deplete the
microsponges before the application.
• The spherical structure of microsponges should not
collapse.
• Polymer design and payload of the microsponges for
the active must be optimized for required release rate for
given time period.
• It should be stable in contact with polymerization
catalyst and conditions of polymerization.
PREPARATION OF MICROSPONGE
Drug loading in microsponges can take place in
two ways, one-step process or by two-step process as
discussed in liquid-liquid suspension polymerization and
quasi emulsion solvent diffusion techniques which are
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based on physicochemical properties of drug to be
loaded.
Liquid-liquid suspension polymerization
The porous microspheres are prepared by
suspension polymerization method in liquid-liquid
systems. In their preparation, the monomers are first
dissolved along with active ingredients in a suitable
solvent solution of monomer and are then dispersed in
the aqueous phase, which consist of additives (surfactant,
suspending agents, etc.). The polymerization is then
initiated by adding catalyst or by increasing temperature
or irradiation.
The various steps in the preparation of microsponges are
summarized as
 Selection of monomer or combination of monomers.
 Formation of chain monomers as polymerization
begins.

Formations of ladders as a result of cross linking
between chain monomers.
 Folding of monomer ladder to form spherical
particles- Agglomeration of microspheres, which give
rise to formation of bunches of microspheres.
 Binding of bunches to form microsponges.
Quasi-emulsion solvent diffusion
This is a two-step process where the
microsponges can be prepared by quasiemulsion solvent
diffusion method (Fig.4) using the different polymer
amounts. To prepare the inner phase, Eudragit RS 100
was dissolved in ethyl alcohol. Then, drug can be then
added to solution and dissolved under ultrasonication at
35oC. The inner phase was poured into the PVA solution
in water (outer phase). Following 60 min of stirring, the
mixture is filtered to separate the microsponges. The
microsponges are dried in an air heated oven at 40oC for
12 Hr and weighed to determine production yield.
MECHANISM OF DRUG RELEASE
Pressure triggered systems
Microsponge system releases the entrapped
material when pressurized/rubbed; the amount released
depends upon various characteristics of the sponge. By
varying the type of material and different process
variables, the microsponge best suited for a given
application may be optimized. When compared with
mineral oil containing microcapsules, mineral oil
containing microsponge showed much more softening
effect. The duration of emolliency was also much more
for the microsponge systems.
Temperature triggered systems
Some entrapped active ingredients can be too
viscous at room temperature to flow spontaneously from
microsponges onto the skin. Increased in skin
temperature can result in an increased flow rate and
hence release. So it is possible to modulate the release of
substances from the microsponge by modulation of
temperature. For example, viscous sunscreens were found
to show a higher release from microsponges when
exposed to higher temperatures; thus a sunscreen would
be released from a microsponge only upon exposure to
the heat from the sun.
pH triggered systems
Triggering the pH-based release of the active
can be achieved by modifying the coating on the
microsponge. This has many applications in drug
delivery.
Solubility triggered system
Microsponges loaded with water-soluble
ingredients like anti-prespirants and antiseptics will
release the ingredient in the presence of water. Presence
of an aqueous medium such as perspiration can trigger
the release rate of active ingredients. Thus release may be
achieved based on the ability of the external medium to
dissolve the active, the concentration gradient or the
ability to swell the microspore network.
PHYSICAL CHARACTERIZATION OF MICRO
SPONGES
Particle size determination
Particle size analysis of loaded and unloaded
microsponges can be performed by laser light
diffractometry or any other suitable method. The values
can be expressed for all formulations as mean size range.
Cumulative percentage drug release from microsponges
of different particle size will be plotted against time to
study effect of particle size on drug release. Particles
larger than 30μm can impart gritty feeling and hence
particles of sizes between 10 and 25μm are preferred to
use in final topical formulation.
Morphology and surface topography of microsponges
For morphology and surface topography,
prepared microsponges can be coated with gold–
palladium under an argon atmosphere at room
temperature and then the surface morphology of the
microsponges can be studied by scanning electron
microscopy (SEM).
Determination of loading efficiency and production
yield20
The loading efficiency (%) of the microsponges can be
calculated according to the following equation:
Actual Drug Content in Microsponges
Loading efficiency = -----------------------------------------------X 100 (1)
Theoretical Drug Content
The production yield of the micro particles can be
determined by calculating accurately the initial weight of
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the raw materials and the last weight of the microsponge
obtained.
Practical mass of microsponges
Production Yield =---------------------------------------------X 100… (2)
Theoretical mass (Polymer+drug)
Determination of true density
The true density of microparticles is measured
using an ultra-pycnometer under helium gas and is
calculated from a mean of repeated determinations.
Characterization of pore structure
Pore volume and diameter are vital in
controlling the intensity and duration of effectiveness of
the active ingredient. Pore diameter also affects the
migration of active ingredients from microsponges into
the vehicle in which the material is dispersed.
Compatibility studies
Compatibility of drug with reaction adjuncts can
be studied by thin layer chromatography (TLC) and
Fig 1. Structure of Microsponge
Fourier Transform Infra-red spectroscopy (FT-IR). Effect
of polymerization on crystalline of the drug can be
studied by powder X-ray diffraction (XRD) and
Differential Scanning Colorimetry (DSC). For DSC
approximately 5mg samples can be accurately weighed
into aluminum pans and sealed and can be run at a
heating rate of 15oC/min over a temperature range 25–
430oC in atmosphere of nitrogen.
Polymer/monomer composition
Factors such as microsphere size, drug loading
and polymer composition govern the drug release from
microspheres. Polymer composition of the MDS can
affect partition coefficient of the entrapped drug between
the vehicle and the microsponge system and hence have
direct influence on the release rate of entrapped drug.
Release of drug from microsponge systems of different
polymer compositions can be studied by plotting
cumulative % drug release against time.
Fig 2. Reaction vessel for Microsponge Preparation by
Liquid Liquid suspension method.
Fig 3. Method of Quasi-emulsion solvent diffusion
Table 1. Applications of Microsponge
Active agents
Sunscreens
Anti-acne e.g. Benzoyl peroxide
Anti-inflammatory e.g. hydrocortisone
Applications
Long lasting product efficacy, with improved protection against
sunburns and sun related injuries even at elevated concentration and
with reduced irritancy and sensitization.
Maintained efficacy with decreased skin irritation and sensitization.
Long lasting activity with reduction of skin allergic response and
dermatoses.
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Antifungals
Antidandruffs e.g. zinc pyrithione, selenium
sulfide
Antipruritics
Skin depigmenting agents e.g. hydroquinone
Rubefacients
Sustained release of actives.
Reduced unpleasant odor with lowered irritation with extended safety
and efficacy.
Extended and improved activity.
Improved stabilization against oxidation with improved efficacy and
aesthetic appeal.
Prolonged activity with reduced irritancy greasiness and odor.
Table 2. Marketed formulations of Microsponge
Product name
Manufacturer
Advantages
Retinol cream
Biomedic
The retinol molecule is kept in the microspongesystem to protect the
potency of the vitamin A. This helps to maximize retinol dosage while
reducing the possibility of irritation. Retinol is a topical vitamin A derivative which helps maintain healthy skin, hair and mucous membranes.
Salicylic Peel 20
Biophora
Deep BHA peeling agent for (professional use only): Salicylic acid 20%,
Microsponge Technology, Excellent exfoliation and stimulation of the skin
for more resistant skin types or for faster results. Will dramatically improve
fine lines, pigmentation, and acne concerns.
Dermalogica Oil
John and Ginger
Exclusive skin response complex soothes and purifies, provides effective
Control Lotion
Dermalogica Skin
skin hydration, without adding excess oil; eliminate shine for hours with
Care Products
Dermalogica Oil Control Lotion. Oil Control Lotion is a feather-light lotion, formulated with oil absorbing Microsponge technology and hydrat-ing
botanicals.
Oil free matte
Dermalogica
The naturally antiseptic Skin Response Complex helps soothe and purify
block spf20
the skin Shield skin from damaging UV rays and control oil production
with this invisible sunscreen. Microsponge technology absorbs oil,
maintaining an all-day matte finish and preventing shine without any
powdery residue. Oil free formula contains soothing Green Tea to help
calm inflammation caused by breakouts. Contains no artificial fragrance or
color. Cornstarch and Vinyl Dimethicone/ Methicone Silsesquioxane
Cross-polymer act as microsponges to absorb excess surface oils on skin.
Dissolution studies
Dissolution profile of microsponges can be
studied by use of dissolution apparatus USP XXIII with a
modified basket consisted of 5μm stainless steel mesh.
The speed of the rotation is 150 rpm. The dissolution
medium is selected while considering solubility of
actives to ensure sink conditions. Samples from the
dissolution medium can be analyzed by suitable
analytical method at various intervals.
CONCLUSION
A Microsponge Delivery System can entrap
wide range of actives and then release them onto the skin
over a time and in response to trigger. It is a unique
technolo-gy for the controlled release of topical agents
and con-sists of microporous beads loaded with active
agent and also use for oral as well as biopharmaceutical
drug delivery. A Microsponge Delivery System can
release its active ingredient on a time mode and also in
response to other stimuli. Thus microsponge has got a lot
of po-tential and is a very emerging field which is needed
to be explored.
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