Microsponge Drug Delivery System

1. MICROSPONGE DRUG DELIVERY SYSTEM
PRESENTED BY
Karad B. B.
M Pharm- I Sem
GUIDED BY
Mrs. Barhate A.N.
SVPM’S
College of Pharmacy,
Malegaon (BkII) Tal.Baramati, Dist. Pune
2015-2016
1

2. CONTENTS
1) Introduction
2) Need of microsponge delivery system
3) Methods of preparation
4) Characteristics of microsponges
5) Release mechanism
6) Advantages & limitations
7) Applications
8) Evaluation Parameters
9) Marketed formulations
10) References
2

3. Introduction 1,5,12
MICROSPONGE:
“Microsponges are polymeric delivery
systems composed of porous microspheres. They are tiny
sponge-like spherical particles with a large porous
surface.”
Microsponge is recent novel technique for control release
and target specific drug delivery system.
They are desire to deliver API efficiently at the minimum
dose and also to enhance stability, reduce side effect and
modify drug release.
Typically in 5-25 µm in diameter.
3

4. Microsponge as Topical drug delivery
 The human skin is a large and complex
organ that protects internal tissue from
environmental exposure. As the interface
between the organism and the external
world, the skin is susceptible to injuries
from the environment or from other
organisms.
 Topical drug delivery systems are
formulated either to give local effect or to
enter in to the systemic circulation, where
skin serves as the portal of entry to the
drug and various formulations made
available in the market are creams, gels,
lotions, ointments etc.
Skin
4

5.  Main drawbacks of topical preparations for local action are they
may readily absorbed and hence, less duration of action and
decreased activity.
 Similarly topical preparations for systemic action have drawback
like drug doesn’t reaches the systemic circulation in sufficient
amounts.
To overcome this problems MDS technique plays imp. Role.
 A Microsponge Delivery System (MDS) is patented, highly
cross-linked, porous, polymeric microspheres that can entrap
wide range of actives and then release them with desired rate.
This system is applicable for the improvement of performance of
topically applied drugs.
 When microsponge delivery system applied to the skin, the
release of drug can be controlled through diffusion or other
variety of triggers, including rubbing, moisture, pH, friction, and
skin temperature.
 Thus the microsponge should remain maximum time at the skin
and below the epidermis and release the medicament slowly.
5

6. Typical view of Microsponges
Fig.Highly porous nature of
Microsponge
Fig.Retinol entrapped in
Microsponge 6

7. NEED FOR MICROSPONGE DELIVERY SYSTEM
 Microsponges consist of non-collapsible structures with porous
surface through which active ingredients are released in a
controlled manner.
 Their characteristic feature is the capacity to adsorb or“load”
a high degree of active materials into the particle and on to its
surface.
 To prevent excessive accumulation of ingredients within the
epidermis and the dermis.
 Controlled release of drug on to epidermis does not enter the
systemic circulation in significant amounts.
7

8. METHODS OF MICROSPONGE
PREPARATION1,4,6,11,23
 Drug loading in microsponges can take place in two
ways, one-step process or by two-step process ; based
on physico-chemical properties of drug to be loaded.
Following techniques are commonly used
 Liquid-liquid suspension polymerization
 Quasi-emulsion solvent diffusion
8

9. Preparation of microsponge
Drug loading in microsponge
One step
process
Two step
process
Liquid
-liquid suspension polymerisation
Quasi emulsion solvent diffusion
Based on physico-chemical properties of drug to be loaded
9

10. Liquid-liquid suspension polymerization
• Microsponges are prepared by suspension polymerization process
in liquid-liquid systems (one-step process).
• 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. to aid in formation of
suspension).
• Once the suspension is established with distinct droplets of the
preferred size then, polymerization is initiated by increasing
temperature as well as irradiation.
• After polymerization process is complete, the liquid is removed
which is permeate within preformed microsponges then,
incorporates the variety of active substances like anti fungal, anti
acne, anti inflammatory etc. which act as a topical carriers.
10

11. 1. LIQUID-LIQUID SUSPENSION POLYMERIZATION
Fig.:- Reaction vessel for microsponge preparation by liquid-
liquid Suspension Polymerization 11

12. 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.
Fig. Steps in the preparation of microsponges 12

13. Quasi-emulsion solvent diffusion:
• Porous microspheres (microsponges) are also prepared by a
quasi-emulsion solvent diffusion method (two-step process)
using an internal phase containing polymer such as eudragit
which is dissolved in ethyl alcohol.
• Then, the drug is slowly added to the polymer solution and
dissolved under ultra-sonication at 35ºC and plasticizer such as
triethylcitrate (TEC) is added in order to aid the plasticity.
• The inner phase is then poured into external phase containing
polyvinyl alcohol and distilled water with continuous stirring for
2 hours.
• Then, the mixture is filtered to separate the microsponges. The
product (microsponges) was washed and dried in an air- heated
oven at 50°C for 24 hr.
13

14. 2. QUASI-EMULSION SOLVENT DIFFUSION
Fig.: Preparation of microsponges by quasi emulsion solvent
diffusion method
14

15. o CHARACTERISTICS OF MICROSPONGES10,15,17
 Microsponge formulations are stable over range of pH 1 to
11.
 It is stable at the temperature up to 130º c.
 They are compatible with most vehicles and ingredients.
 They are self sterilizing as their average pore size is
0.25μm where bacteria cannot penetrate.
 Microsponge formulations have high entrapment upto 50
to 60%.
 It is free flowing and can be cost effective reduced
irritation and hence improved patient compliance.
15

16. Drug explored in Microsponge drug delivery
system 1,17
 Ibuprofen
 Fluconazole
 Benzoyl peroxide
 Ketoprofen
 Paracetamol
 Dicyclomine
 Flurbiprofen
 Ketoconazole
 Tretinoin
 Trolamine
 Retinol
 Salicylic acid 16

17. CHARACTERISTICS OF MATERIALS ENTRAPED
IN MICROSPONGES10,23,15,17
 They should be completely miscible in monomer.
 They should be water immiscible or at most only
slightly soluble.
 They should be inert to monomers.
 They should be stable in contact with polymerization
catalyst and conditions of polymerization
Mostly liquid or soluble ingredients can be entrapped In the
microsponge.
17

18. Release Mechanisms2,4,17,6
Pressure
Temperature change
Solubility
pH triggred system
18

19. Pressure:
 Rubbing/ pressure applied can release active
ingredient from microsponges onto skin. The amount
released depends upon various characteristics of the
sponge.
Temperature change:
•Some entrapped actives 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.
19

20. Solubility:
 Microsponges loaded with water-soluble ingredients like
anti-perspirants and antiseptics will release the
ingredient in the presence of water.
 The release can also be activated by diffusion taking into
consideration the partition coefficient of the ingredient
between the microsponges and the outside system.
pH triggered systems:
 Triggering the pH-based release of the active can be
achieved by modifying the coating on the microsponge.
20

21. ADVANTAGES OF MICROSPONGE1,2,5,15
Microsponge systems are non-irritating, non-mutagenic,
non-allergenic and non-toxic.
Improved formulation flexibility.
Extended release of drug continuous upto 12 hours.
Reduce irritation and improve patient complience.
Microsponge drug delivery can improve bioavailability
of drug.
21

22. ADVANTAGES OF MICROSPONGE
They have better thermal, physical and chemical
stability.
Allows incorporation of immiscible product.
Advance oil control.
Easy to formulate.
22

23. LIMITATIONS2,5
 The preparation methods usually use organic solvents
as porogens, which pose an environmental hazard, as
some may be highly inflammable, posing a safety
hazard.
 In some cases, the traces of residual monomers have
been observed, which may be toxic and hazardous to
health.
23

24. Sr.No. Active Agents Applications
1. Sunscreens Improved Protection Against
Sunburns and Sun Related Injuries.
2. Anti-acne:
E.g. Benzoyl peroxide
Maintained Efficacy with Decreased
Skin Irritation and Sensitization.
3. Anti-inflammatory:
E.g. hydrocortisone
Long Lasting Activity With
Reduction of Skin Allergic Response
and Dermatoses.
4. Anti-dandruffs:
E.g. zinc pyrithione,
selenium sulfide.
Reduced Unpleasant Odour with
Lowered Irritation with Extended Safety
and Efficacy .
Applications2,3,11
24

25. Sr.No. Active Agent Applications
5. Antipruritics Extended and improved activity.
6. Skin depigmenting:
E.g.hydroquinone.
Improved stabilization against
oxidation with improved efficacy and
aesthetic agents .
7. Rubefacients Prolonged activity with reduced
irritancy, greasiness and odour.
8. Anti-fungals Sustained release of active
ingredients.
Applications
25

26. Evaluation parameters1,4,6,18
Particle size (Microscopy)
Morphology and Surface topography
Determination of true density
Loading efficiency and production yield
Characterization of pore structure
Compatibility studies
Resiliency (viscoelastic properties)
Drug release study
26

27.  Particle size analysis of loaded and unloaded microsponges can
be performed by laser light diffractometer 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 must 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.
1. Particle size determination :
27

28.  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). SEM of a fractured microsponge
particle can also be taken to illustrate its ultra structure.
2. Morphology and surface topography of
microsponges :
The true density of microparticles is measured using an ultra-
pycnometer under helium gas and is calculated from a mean of
repeated determinations.
3. Determination of true
Density :
28

29. 4. Determination of loading efficiency and
production yield :
 The loading efficiency (%) of the microsponges can be
calculated according to the following equation:
Loading efficiency =
Actual drug in microsphere
Therotical drug concentration
100
 The production yield of the microparticles can be
determined by following equation:
Production yield =
Practical mass
Therotical mass
100
29

30. 5. Characterization of pore structure :
 Mercury intrusion porosimetry can be employed to study
effect of pore diameter and volume with rate of drug
release from microsponges.
 Porosity parameters of microsponges such as intrusion–
extrusion isotherms, pore size distribution, total pore
surface area, average pore diameters, shape and
morphology of the pores, bulk and apparent density can be
determined by using mercury intrusion porosimetry.
30

31. 6. Compatibility studies :
 Compatibility of drug with reaction adjuncts can be
studied by thin layer chromatography (TLC) and Fourier
Transform Infra-red spectroscopy (FT-IR). Effect of
polymerization on crystallinity of the drug can be studied
by powder X-ray diffraction (XRD) and Differential
Scanning Colorimetry (DSC).
31

32. 7. Resiliency :
 Resiliency (viscoelastic properties) of Microsponges can
be modified to produce beadlets that is softer or firmer
according to the needs of the final formulation. Increased
cross- linking tends to slow down the rate of release.
In vitro release studies can be performed using United
States Pharmacopeial (USP) dissolution apparatus
equipped with a modified basket consisted of 5 μm
stainless steel mesh at 37°C. The release medium is
selected according to the type of formulation that is, topical
or oral, while considering solubility of active ingredients to
ensure sink conditions.
8.Invitro Drug Release study :
32

33. Examples of MDS with their formulation 6
33
MDS Drugs Disease treatment
Gels Benzoyl peroxide Anti-acne Treatment
Fluconazole Anti-fungal
Diclofenac Sodium Anti Inflammation
Terbinafine HCL Anti-fungal
Lotions Benzoyl Peroxide Anti-acne Treatment
Creams Hydroquinone and Retinol Melanoma
Other Ibuprofen NSAID
Mefenamic acid Rhumatoid arthritis

34. Marketed formulation of the MDS1,3,11,18
Product Name Active Ingredient Treatment Manufacturer
Retin-A-Micro 0.1% and 0.4%
tretinoin in an aq.
gel.
Acne vulgaris Ortho-McNeil
Pharmaceutical, Inc.
Cerac Cream,
0.5%
0.5% flurouracil Actinic Keratoses
(AK).
Dermik Laboratories,
Inc.
Berwyn, PA 19312 USA
Oil Control
Lotion
Natural antibiotics Acne-Prone, oily skin
conditions.
Fountain Cosmetics
Ultra Guard Dimethicone Protect a baby’s skin
from diaper rash.
Scott Paper
Company.
Salicylic Peel 20
Salicylic Peel 30
Salicylic acid 20%
Salicylic acid 30%
Improve fine lines,
pigmentation and acne
concerns.
Biophora.
34

35. Product Name Active Ingredient Treatment Manufacturer
Lactrex™ 12%
Moisturizing
Cream
12% lactic acid as
the neutral
ammonium salt,
ammonium lactate.
Long lasting
moisturization.
SDR Pharmaceuticals,
Inc., Andover, NJ
U.S.A. 07821.
EpiQuin Micro Retinol and
Hydroquinone
Minimize skin irritation,
Reduce age spot, sun spot
etc.
Skin Medica
Inc.
Line eliminator
Dual Retinol
Facial Treatment
Retinol
(vitamin A)
Diminish wrinkle,
appearance of fine lines
etc.
Avon
Sportscream RS
and XS
Topical analgesic,
anti-inflammatory
and counterirritant.
Management of
Musculoskeletal
conditions.
Embil
Pharmaceutical
Co.Ltd.
Micro peel plus /
Acne peel
Salicylic acid in
forms of
Microcrystals.
Remove all dead cells
doing no damage to skin. Biomedic.
35

36. Ultra guard
Cerac creamEpiQuin Micro
Neutrogena Shine stopper
Oil control
Dermalogica
Oil control
Murad
Moisturizing cream Image
Sunscreen
Marketed Preparations
36

37. 1) Patel A, Upadhyay P. Microsponges As The Versatile Tool For
Topical Route: A Review. Int J Pharm Sci. Res. 2012;3(9): 2926-
2937.
2) Kale S, Shalini R. Microsponge: Comprehensive Review of
Application. Int J Pharm Bio Sci. 2013;3(1):214-226.
3) Shaha V, Jain H. Microsponge Drug Delivery: A Review. Int J
Res Pharm Sci. 2010;1(2):212-218.
4) Patel EK, Oswal RJ. Nanosponge And Micro Sponges: A Novel
Drug Delivery System. Int J Res. Pharm Chem. 2012;2(2):237-
243.
5) Hussain H, Juyal D. Microsponges: An Overview. Ind J Novel
Drug Delivery 2014;6(3):198-207.
6) Sinkar NB, Gondkar SB, Saudagar RB. Microsponge A
Innovative Strategy For Drug Delivery System, Current Status
And Future Prospects-A Review. Int J Inst Pharm Life Sci.
2015;5(3):226-242.
References
37

38. 7) Arora N, Agarwal S, Murthy RS. Latest Technology Advances In
Cosmaceuticals. Int J Pharm Sci. Drug Res. 2012;4(3):168-182.
8) Hussain H, Dhyani A, Juyal D. Formulation And Evaluation of
Gel-Loaded Microsponges Of Diclofenac Sodium For Topical
Delivery. The Pharma Innovation J. 2014;3(10):58-63.
9) Mahajan A, Jagtap L, Chaudhari A. Formulation And Evaluation
of Microsponge Drug Delivery System Using Indomethacin. Int
Res J Pharm. 2011;2(10):64-69.
10) Saroj Kumar Pradhan. Microsponges As The Versatile Tool For
Drug Delivery System: A Review. Int J Res Pharm Chem.
2011;1(2);243-258.
11) Yerram C, Shaik F, Rubia Y. Microsponges: A Novel Drug
Delivery System For Controlled Delivery of Topical Drugs. Int J
Pharm Res. 2012;2(2):79-86.
12) Pandey P , Jain V, Mahajan SC. A Review: Microsponge Drug
Delivery System. Int J Bio Pharm. 2013;4(3):225-230.
38

39. 13) Charde MS, Ghanawat PB. Microsponge A Novel New Drug
Delivery System: A Review. Int J Adv Pharm. 2013;2(6):64-70.
14) Aloorkar NH, Kulkarni AS. Microsponge As Innovative Drug
Delivery System. Int J Pharm Sci. 2012;5(1):1597-1606.
15) Makwana R, Patel H, Patel V. Microsponge For Topical Drug
Delivery System. Int J Pharm Tech. 2014; 5(4): 2839-2851.
16) Kumar R, Sharma SK. Microsponge Drug Delivery Systems For
Novel Topical Drug Delivery. Int J Pharm Sci Letters. 2014;
4(3):384-390.
17) Jadhav N, Patel V, Mungekar S. Microsponge Delivery System:
An Updated Review, Current Status And Future Prospects. J Sci
Innovative Res. 2013;2(6):1097-1110.
18) Ravi R, Senthilkumar Sk. Microsponges Drug Delivery System:
A Review. Int J Pharm Rev Res. 2013;3(1):6-11.
39

40. 19) Jangde R. Microsponges For Colon Targeted Drug Delivery
System: An Overview. Asian J Pharm Tech. 2011;1(4):87-93.
20) Ravi R, Senthil Kumar SK, Parthiban S. Formulation And
Evaluation of The Microsponges Gel For An Anti Acne Agent For
The Treatment of Acne. Ind J Pharm Sci Res. 2013; 3(1):32-38.
21) D’souza J, More HN. Topical Anti-Inflammatory Gels of
Fluocinolone Acetonide Entrapped In Eudragit Based
Microsponge Delivery System. Res J Pharm Tech. 2008;1(4):502-
506.
22) Bhowmik D, Gopinath H. Recent Advances In Novel Topical
Drug Delivery System. The Pharma Innovation. 2012;1(9):12-31.
23) Osmani RA, Aloorkar NH, Ingale DJ. Microsponges Based
Novel Drug Delivery System For Augmented Arthritis Therapy.
Saudi Pharm J 2015.
24) Karthika R, Elango K. Formulation And Evaluation of
Lornoxicam Microsponge Tablets For The Treatment of Arthritis.
Int J Pharm Innovations 2013; 3(2):29-40. 40