Self-Micro Emulsifying Drug Delivery System

SELF – MICRO EMULSIFYING
DRUG DELIVERY SYSTEM
(SMEDDS)
Presented by –
Birupananda Swain
M Pharm Pharmaceutics 1st Year
RA2122254010014
SRM College of Pharmacy,
Kattankulathur , Chennai

MECHANISM OF
ACTION
7.
6.
5.
4.
3.
2.
1.
CONTENTS
INTRODUCTION
WHAT IS SMEDDS ?
TYPES
ADVANTAGES
DISADVANTAGES
COMPOSITIONS
DRUGS USED
13.
11.
10.
9.
8. FORMULATION
EVALUATION TESTS
APPLICATIONS
REFERENCES

INTRODUCTION
→ Now a days, one of the major problems to drug formulation
is poor water solubility of new drugs.
→ More than 40% of all the new drugs are poorly water
soluble.
→ Poor water soluble drugs have low dissolution rate and poor
bioavailability inside the body.
→ So in recent years much attention has been given on using
Self-Micro Emulsifying Drug Delivery Systems.(SMEDDS)

WHAT IS SMEDDS ?
→ Self Micro Emulsifying Drug Delivery System (SMEDDS) are
defined as isotropic mixtures of natural or synthetic oils, surfactants
and co-surfactants.
→ The mixture have a unique ability of forming fine oil-in-water
(o/w) micro emulsions upon mild agitation and dilution in aqueous
media such as GI fluids.
→ SMEDDS is optically clear and thermodynamically stable system
with a droplet size less than 100 nm .
→ This system has shown to improve absorption of drugs due to
small droplet size.( As Micro Emulsion)

TYPES
1. O/W Micro Emulsion
2. W/O Micro Emulsion

ADVANTAGES
1. Improvement in oral bioavailability- SMEDDS present the
drug to GIT in solubilized and micro emulsified form and
increase in specific surface area enable more efficient drug
transport through the intestine leading to improved
bioavailability.
2. Oil phase can work not only as a carrier but also a ‘shield’
to protect the attack and degradation from enzymes.
3. Ease of manufacture and scale-up- SMEDDS require very
simple and economical equipments like simple mixer with
agitator and volumetric liquid filling equipment.

4. Reduction in inter-subject and intra-subject variability
in absorption and food effects- The performance of
SMEDDS is independent of food.
5. Potential to deliver peptides that are processed to
enzymatic hydrolysis in GIT.
6. Useful for both solid and liquid dosage forms.
ADVANTAGES

DISADVANTAGES
1. In vitro model needs further development and validation
before its strength can be evaluated.
2. Chemical instabilities of drugs and high percentage of
surfactant may irritate GIT.
3. Co solvents can migrate into the shells of soft or hard gelatin
capsules, resulting in the precipitation drugs.
4. The precipitation tendency of the drug on dilution may be
high due to the dilution effect of the hydrophilic solvent.
5. Formulations containing several excipients become more
challenging to validate.

COSURFACTANTS
/
COSOLVENTS
OIL SURFACTANTS
COMPOSITION OF SMEDDS
→ SMEDDS is composed of

OIL PHASE
→ Oils from natural sources and their derivatives are used.
→ The oil represents the most important excipient in the
SMEDDS formulations.
→ Oil solubilizes the hydrophobic drug and aids in self
emulsification.
→ Both long chain triglycerides (LCT) and medium chain
triglycerides (MCT) oils with different degrees of saturation have
been used in the design of SMEDDS.

EXAMPLES OF OIL PHASE
1. Triglycerides of long chain fatty acids - Soyabean oil, Peanut oil,
corn oil
2. Triglycerides of medium chain fatty acids - Miglyol 812, Captex
355
3. Vegetable oils derivatives
1) Hydrogenated vegetable oil - Hydrogenated cottonseed oil
2) Mixed Partial Glycerides - Capmul MCM
3) Polyoxylglycerides/Macrogolglycerides - Labrafil 1944CS,
Labrafil M 2125CS , Labrasol , Gelucire 44/14.
4) Ethoxylated glycerides - Cremophor EL, Cremophor
RH40, Cremophor RH60.

SURFACTANTS
→ Surfactants are one of the important components of
SMEDDS because they are responsible for forming a stable
emulsion upon dilution and stabilize the internal phase in an
emulsion.
→ Surfactants with an HLB value of more than 12 is
necessary in SMEDDS.
→ Emulsifier of natural origin are not widely used because of
their poor self emulsification property.

SURFACTANTS
→ Emulsifier of natural origin are not widely used because of
their poor self emulsification property.
→ Non-ionic surfactants are less toxic and are widely used.
→ Usually the surfactant concentration ranges between 30-60 %
w/w to form a stable SMEDDS.
→ Increase in surfactant concentration causes a decrease in
droplet size thus surfactant molecules stabilizes at the oil-water
interface and if surfactant concentration is less then it causes
enhanced water penetration into oil droplets leading to
breakdown of oil droplets.

CLASSIFICATION OF SURFACTANTS
1. ANIONIC
Classification is based on the nature of the hydrophilic group within the
molecules -
→ Where the hydrophilic group carries a negative charge
such as carboxyl (RCOO-), sulphonates (RSO3-) or
sulphate (ROSO3 -) are known as anionic surfactants.
Examples – Potassium laurate , Sodium lauryl sulphate.

2.CATIONIC
→ These are the surfactants where the hydrophilic group carries a
positive charge.
Example – Quaternary ammonium compounds.
3.AMPHOTERIC
→ Here the hydrophilic group carries both the positive and
negative charges.
→ It is also called as zwitterionic surfactants.
Examples – Sulfobetaines, Cocoamphoacetate

4.NONIONIC
→ The hydrophilic group do not carry any charge in case of non ionic
surfactants.
→ The water solubility of these surfactants are due to hydrogen
bonding.

CO-SURFACTANTS
→ Co-surfactants are used to enhance the effectiveness of a
surfactant.
→ They are added to reduce the interfacial tension of the oil
and water phase and increases the fluidity of interface .
→ They destroy liquid crystalline or gel structure which would
prevent the formation of micro emulsion.
→ Often used to increase the oil solubilizing capacity of the
microemulsions.
Examples –PEG 200/400/600, Transcutol P, Ethanol,
Propylene glycol.

CO-SOLVENTS
→ Co-Solvents promotes the formation of low viscosity
microemulsions.
→ They helps in the dissolution of large quantities of either the
hydrophilic surfactant or the drug in the lipid base.
Examples – Ethanol, Glycerine, Polyethylene glycol.

DRUGS CHARACTERISTICS FOR SMEDDS
The drugs selected for SMEDDS preparation should have
following characteristics –
→ It should be BCS class II and class IV drug. ( Low solubility )
→ Should be soluble in oil phase.
→ Dose of the drug should be less.
→ Log P value of the drug should be greater than 5.

FORMULATION
→ The solubility of drug in different oil, surfactant and co-
surfactant was checked then the suitable composition is selected
based on the solubility of the drug and preparation of phase
diagrams.
→ Phase diagram study is most before doing the formulation.

PHASE DIAGRAM
→ Phase diagrams were constructed to obtain the proportion of
components that result in maximum microemulsion existance
area.
→ A Pseudo Ternary phase Diagram is used for optimization of
any typical emulsion.
→ The diagrams were constructed with oil, surfactant/co-
surfactants (Smix) and water (pseudo-ternary phase diagram) by
using water titration method at room temperature.
→ The procedure consists of preparing solutions of different ratio
of surfactant to co-surfactant by weight such as 1:1, 2:1, 3:1 .

CONTINUES...
→ Each of these solution are then taken and used to prepare a
mixture of oil and Smix in a ratio of 1:9, 2:8, 3:7, 4:6, 5:5,
6:4, 7:3, 8:2, 9:1 and then vortexed for 5 min and placed in
oven at 50° c for 1 hour.
→ All the mixtures are placed at room temperature for 24
hours.
→ Water from 5% to 95% of the mixtures are added at 10-15
min interval to each of the mixture under stirring on magnetic
stirrer.
.

→ After each water addition mixtures were observed for their
appearance.
→ The solution is vortexed for 5 min and placed at 50° c for 1
hour.
→ It is observed for turbidity or clearness, if turbidity
(cloudiness) is observed then it is a coarse emulsion and if clear
isotropic solution then it is a micro emulsion.
CONTINUES...

Self-Micro Emulsifying Drug Delivery System

MECHANISM OF ACTION
→ Self emulsification occurs when the entropy change that
favours dispersion is greater than the energy required to
increase the surface area of the dispersion.
→ For emulsification to take place, it is important for the
interfacial structure to no resistance against surface
shearing.
→The interface between the oil and aqueous continuous
phases is formed upon addition of a binary mixture (oil /
non-ionic surfactant ) to water .
→ Then the solubilization occurs within the oil phase, as a
result of aqueous penetration through the interface .

→ Aqueous penetration will lead to the formation of the
dispersed liquid crystals (LC) phase .
→ Following gentle agitation of the self emulsifying system,
water rapidly penetrates into the aqueous cores leading to
interface disruption and droplet formation .
→ The liquid crystal phase is considered to be responsible for
the high stability of the resulting microemulsion against
coalescence.
MECHANISM OF ACTION

EVALUATION TESTS
1. Thermodynamic stability studies
2. Dispersibility Test
3. Turbidimetric Evaluation
4. Droplet Size
5. Viscosity Measurement

1. THERMODYNAMIC STABILITY STUDIES
TEMPERATURE STABILITY –
→ The preparations are diluted with purified distilled water &
then for temperature stability they are kept at a different
temperature range . (4° C , 25° C and 40° C )
→ Then it is observed for any phase separation, flocculation or
precipitation.
CENTRIFUGATION –
→ The prepared SMEDDS is centrifuged at a rate of 3000 rpm
for 5 minutes then checked for homogeneity or uniformity.

2. DISPERSIBILITY TEST
→ The efficiency of self emulsification of the micro emulsion
checked by using a standard USP dissolution apparatus.
→ 1 ml of each formulation are taken
→ 500 ml of water is taken as medium
→ Temperature is maintained at 37 ± 0.5° C.
→ Paddle rotated at 50 rpm.
Observations are like following –
• Grade A: Rapidly forming (within 1 min) nanoemulsion ,
having a clear or bluish appearance.

• Grade B: Rapidly forming, slightly less clear emulsion,
having a bluish white appearance.
• Grade C: Fine milky emulsion that is formed within 2 min.
• Grade D: Dull, grayish white emulsion having slightly oily
appearance that is slow to emulsify (longer than 2 min).
• Grade E: Formulation, exhibiting either poor or minimal
emulsification with large oil globules present on the surface.
• Grade A and Grade B formulation will remain as
nanoemulsion when dispersed in GIT, while formulation
falling in Grade C could be recommend for SMEDDS
formulation.
CONT..

3. TURBIDIMETRIC EVALUATION
→ Mainly the increasing turbidity is measured by a
Nepheloturbidimeter.
→ Emulsion is taken with a medium of 0.1m HCl & continuously
stirred at 50 rpm at a fixed temperature & turbidity is measured
according to time.

→ This is a crucial factor in self emulsification performance
because it determines the rate and extent of drug release as
well as the stability of the emulsion.
→ Photon correlation spectroscopy, microscopic techniques
or a Coulter Nanosizer are mainly used for determination of
the emulsion droplet size.
4. DROPLET SIZE

5. VISCOSITY MEASUREMENT
→ The Rheological properties of the micro emulsion are
evaluated by Brookfield viscometer.
→ This viscosities determination confirm whether the system
is w/o or o/w.
→ If system has low viscosity then it is o/w type of emulsion
and if a high viscosity then it is w/o emulsion.

APPLICATIONS
1. Solubilization in SMEDDS
SMEDDS are usually efficient solubilizers of substances
of a wide range of lipophilicity .
2. Sustain release from SMEDDS
Microemulsion composition is important for the drug
release rate.
3. Increase the bioavailability of drug
Many lipophilic drugs are having low solubility and
bioavailability ,there bioavailability increased by
SMEDDS formulation.

REFERENCES
1. Self Micro emulsifying Drug Delivery System : A Lipid
Based Drug Delivery System, IJPSR (2016), Vol. 7, Issue 2
2. A Self-Micro emulsifying Drug Delivery System
(SMEDDS) Maulik J. Patel, Sanjay S. Patel, Natvarlal M.
Patel, Madhabhai M. Patel
3. Tang J: Self-Emulsifying Drug Delivery Systems: strategy
for improving oral delivery of poorly soluble drugs, Cur
Drug Th 2007; 2;85-93
4. Self Micro Emulsifying Drug Delivery System (SMEDDS):
A Review Sagar Savale, Shailesh Chalikwa

Self-Micro Emulsifying Drug Delivery System

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