self micro emulsifying drug delivery system

Submitted to:
Dr. J. Josephine Leno Jenita
Asst. Professor,
Department of Pharmaceutics,
College of Pharmaceutical Sciences, DSU
Dayananda sagar college of Pharmacy,
Banglore.
Presented by:
Arpitha.B. M
M Pharm (I SEM),
Department of Pharmaceutics,
College of Pharmaceutical Sciences, DSU
Dayananda Sagar College of Pharmacy,
Banglore.
Self micro emulsifying drug
delivery system

Contents
• Introduction
• Need for SMEEDS
• Difference between SMEDDS & SEDDS
• Advantages and disadvantages
• Formulation aspects of SMEDDS
• Application
• Reference
2COPS DSU Department of Pharmaceutics

Introduction
SMEDDS are defined as isotropic mixtures of natural or
synthetic oils, solid and liquid surfactants or alternatively, one
or more hydrophillic solvents and co-solvents/surfactants, that
have a unique ability of forming fine oil-in-water (o/w) micro
emulsions upon mild agitation followed by dilution in aqueous
media, such as GI fluids.
• These are micro emulsion containing particle size from 10-
100nm.
• Micro emulsion have been succesively used to improve the
solubility, chemical stability and oral bioavailability of poorly
water soluble drugs. (class II and IV as per BCS clasification)

Comparision b/w emulsion &
microemulsion.
Emulsion Microemulsion
1. Emulsion consists of roughly spherical
droplets of one phase dispersed to other.
1. They constantly evolve between
various structures ranging from droplet
to bi- continous structure.
2. They particle or non transparent as the
particle/droplet size varies from 1-20 mm
2. They are transparent as the particle/
droplet size is only 10-100 nm.
3. Formulation requires shaking. 3. It’s a constant formulation.
4. They are thermodynamically unstable. 4. They are thermodynamically stable.
5. They are viscous formulation. 5. They can accommodate 20-40%
without increase in viscosity.

Comparision between SEDDS and
SMEDDS
SEDDS SMEDDS
1. It is the mixture of oil, surfactant and
drug.
1. It is a mixture of oil, surfactant, co-
surfactant and drug.
2. Droplet size is 100-300 nm 2. Droplet size is less than 100 nm
3. It is turbid in nature. 3. It is transparent in nature.
4. It is thermodynamically not stable. 4. It is thermodynamically stable.
5. Ternary phase diagram are use in
optimization
5. Pseudo ternary phase diagram are used
for optimization.
6. Concentration of oil 40-80% 6. Less than 20%

Need for SMEDDS
• The main purpose is to prepare SMEDDS for “oral
bioavailability enhancement of a poorly water
soluble drug”.
• Used to improve the oral absorption of highly
lipophilic drug compounds.
• 40% of the NCE comes under class II & class IV

BIOPHARMACEUTICAL CLASSIFICATION
SYSTEM (BCS)
CLASS I
HIGHLY SOLUBLE
HIGHLY PERMEABLE
CLASS II
POORLY SOLUBLE
HIGHLY PERMEABLE
CLASS III
HIGHLY SOLUBLE
POORLY PERMEABLE
CLASS IV
POORLY SOLUBLE
POORLY PERMEABLE
 40% NCE belongs to BCS Class II and Class IV

Mechanism
• SEDDS emulsify spontaneously to produce fine o/w
emulsions when introduced into aqueous phase under
gentle agitation, provided by the peristaltic motility
in GI tract, then absorbed by lymphatic pathways.
• Self-emulsification occurs when the entropy change
that favors dispersion is greater than the energy
required to increase the surface area of the dispersion.
• The interface between the oil and aqueous phases is
formed upon addition of a binary mixture.
• This is followed by the solubilization of water within
the oil phases as a result of aqueous penetration
through the interface.

• Following gentle agitation of the self emulsifying
system, water will rapidly penetrate into the aqueous
cores and lead to interface disruptions and droplet
formation.
SEDDS SMEDDS

Advantages over conventional
emulsion
 Thermodynamically stable & easily stored.
 More reproducible blood-time profiles.
 Globule size:2-100nm,better absorption leads to increased
penetration to GIT and bioavailability of drug.
 Optical transparency.
 Can be formulated in various dosage forms.
 Can be autoclaved.
 Solubility of hydrophobic drug.
 Increased bioavailability of the drug.

Advantages
• Improvement in oral bioavailability: Dissolution rate
dependant. Eg: In case of Halofantrine approximately
6-8 fold increase in bioavailability of drug was
reported in comparison to tablet formulation.
• Ease of manufacture and scale-up:
• Reduction in inter-subject and intra-subject variability
and food effects.
• Ability to deliver peptides that are prone to enzymatic
hydrolysis in GI.

• No influence of lipid digestion process as
found in other LDDS.
• Increased drug loading capacity
• Protection of sensitive drug substances.

Disadvantage
1. The drawbacks of this system include chemical
instabilities of drugs and high surfactant
concentrations in formulations (approximately 30-
60%) which irritate GIT.
2. Moreover, volatile co solvents in the conventional
self-micro emulsifying formulations are known to
migrate into the shells of soft or hard gelatin
capsules, resulting in the precipitation of the
lipophilic drugs.
3. The precipitation tendency of the drug on dilution
may be higher due to the dilution effect of the
hydrophilic solvent.

4. One of the obstacles for the development of
SMEDDS and other lipid-based formulations is the
lack of good predicative in vitro models for
assessment of the formulations.
5. Traditional dissolution methods do not work, because
these formulations potentially are dependent on
digestion prior to release of the drug. This in vitro
model needs further development and validation
before its strength can be evaluated.

Composition of SMEDDS
SMEEDS
(isotropic
solution)
Drug
Surfact
ant
Co-
surfact
ant
Oil
phase

1. Role : to solubalise good amount of
lipophilic drug and intestinal lymphatic
uptake of lipophlic drug.
2. Nontoxic and safe components.
3.Oil from natural sources and modified
vegetable oil are suitable. The extension of
micro emulsion generally depends on nature
of oil. This is due to difference in oil
penetration into surfactant layer.
4. Medium chain TGs are preffered than
long chain because they are more
adsorbable, don’t get deposited in the body
and more solubility for lipophilic drugs.
E.g. corn oil, soyabean oil, triglycerides and
fatty acid methyl esters.
1. OIL PHASE

1. SMEDDS are self emulsifying
because of surfactants.
2. They assist in instantaneous formation
of O/W droplet. A little quantity of
surfactant molecules rests upon the
water-air interface and decreases the
water surface tension value (the force per
unit area needed to make available
surface). That is why the surfactant
name: “surface active agent”.
3. They solubalise drug and prevents
precipitation.
4. Non-ionic with high HLB value (e.g.,
Tween, Labrasol, Labrafac CM 10,
Cremophore)
2.SURFACTANT
6. Usual concentration - 30%-60% w/w immediate formation of o/w droplets
and/or rapid spreading of the formulation in the aqueous media.
5. Emulsifiers from Natural origin(Lecithin)- safe.

1.Help to dissolve large amounts of either
the hydrophilic surfactant or the drug in
the lipid base, thus increases the
solubility.
2.Reduces the overall effect of surfactant.
3.Ethanol, Propylene glycol (PG),
Polyethylene glycol (PEG), etc (suitable
for oral administration.
5.Solvents can even act as co surfactants
in micro emulsion systems.
6.Alternately alcohols and other volatile
co solvents have the disadvantage of
evaporating into the shells of the soft
gelatin or hard sealed gelatin capsules in
conventional SMEDDS leading to drug
precipitation.
3. CO- SURFACTANT/
CO SOLVENT

Mainly BCS classification class
II drugs :
• Nifedipine,
• Cyclosporin,
• Digoxin
• Steroids,
• Diazepam
• Artemether
• Carbamazepine
• Griseofulvin
• Glibenclamide
• Haloperidol
• Ibuprofen
• Phenytoin
Sodium
• FOLIC acid
4. DRUG

Other components
• pH adjusters
• Flavours
• Antioxidant agents
– Lipophilic antioxidants(E.g. alpha tocopherol,
Propyl Gallate,Ascorbyl palmitate )
– [ stabilize the oily content of SMEDDS
formulation].
• Consistency builder

Requirement for the formulation
The self micro-emulsification process is specific to
1.The nature of the oil/surfactant pair.
2.The surfactant concentration.
3.Oil/surfactant ratio.
4.The concentration and nature of co-surfactant and
surfactant/co-surfactant.
5.Temperature at which self micro-emulsification occurs.
6.Suitable drug candidate - BCS II classification drugs are
preferred.
Eg: nifidipine, cyclosporin, dixogin and steroids etc.

Screening of excipients: Solubility studies
• Drug has to dissolve in to oil phase(lipophilic part) of
microemulsion.
• Water phase is combined with the surfactant and then
cosurfactant is added slowly with constant stirring
until the system is become transparent.
• The amount of surfactant and co-surfactant to be
added and the parent oil phase that can be
incorporated is determined with the help of pseudo
ternary phase diagram.
• Ultrasonicator can finally used to achieve the desired
range for the dispersed phase.

• It is then allow to equilibrate.
• Gel may be prepared by the addition of the gelling
agent to above micro emulsion.
• Solidification using solid carriers for solid SMEEDS
• Eg: adsorbent material like kaolin (we can directly
adsorb ligquid into adsorbent --- solid).

Ternary diagram

METHODS OF PREPARATION
1. Phase Titration Method
2. Phase inversion Method
1. Phase Titration Method
• dilution of an oil-surfactant mixture with water.(w/o)
• dilution of a water-surfactant mixture with oil.(o/w)
• mixing all components at once. In some systems, the
order of ingredient addition may determine wheather
a microemulsion forms.

2.Phase inversion method
• Phase Inversion Temperature (PIT), i.e., the
temperature range in which an o/w microemulsion
inverts to a w/o type or vice versa or by addition of
excess dispersed phase.
• During phase inversion drastic physical changes
occur including changes in particle size that can
ultimately affect drug release both in vitro and invivo.
• Eg: with increasing temp, the polyoxyethylene group
becomes dehydrated altering critical packing
parameter which results in the phase inversion.

APPLICATIONS
• SUPERSATURABLE SMEDDS (S-SMEDDS): The high
surfactant level typically present in SMEDDS formulation
can lead to GI side effects and a new class of
supersaturable formulations including supersaturable
SMEDDS. (S-SMEDDS) formulations have been
designed and developed to reduce the surfactant side
effects and achieve rapid absorption of poorly soluble
drugs and bioavailability.
Eg: NSAIDS & Ketoprofen.
• PROTECTION AGAINST BIODEGRADATION:
Liquid crystalline phase in SEDDS acts as barrier
between degrading environment and drug.
Eg: proteins and peptides.

• SOLID SMEDDS: SMEDDS are normally prepared
as liquid dosage forms that can be administrated in
soft gelatin capsules, which have some disadvantages
especially in the manufacturing process. An
alternative method is the incorporation of liquid self
emulsifying ingredients into a powder in order to
create a solid dosage form (tablets, capsules). A pellet
formulation of progesterone in SMEDDS has been
prepared by the process of extrusion /spheronization
to provide a good in vitro drug release (100% within
30 min, T50% at 13 min). The same dose of
progesterone (16 mg) in pellets and in the SEDDS
liquid formulation resulted in similar AUC, C max
and T max values.

Marketed Products
COPS DSU Department of Pharmaceutics 30

Reference
1. Tang J: Self-Emulsifying Drug Delivery Systems:
strategy for improving oral delivery of poorly
soluble drugs. Cur Drug Th 2007; 2: 85-93.
2. Spernath A, AserinA (December 2006).
"Microemulsions as carriers for drugs and
nutraceuticals". Adv Colloid Interface Sci 128-130:
47–64. doi:10.1016/j.cis.2006.11.016. PMID
17229398.
3. You tube video on SMEDDS by Dr. Trapti Saxena.

self micro emulsifying drug delivery system

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