SEDDS

SELF-EMULSIFYING DRUG DELIVERY
SYSTEM(SEDDS)
Presented by:
Varun M Girme
(PharmaceuticssemII)
Sinhgad Technical Education Society,
SINHGAD INSTITUTE OF PHARMACY, NARHE, PUNE.
4/15/2015 1SEDDS

NEED FOR NEW APPROACH
WHAT IS SEDDS?
ADVANTAGES OF SEDDS
DISADVANTAGES OF SEDDS
COMPOSITION OF SEDDS
MECHANISM OF SELFEMULSIFICATION
PREPARATION OF SEEDDS
DOSAGE FORMS
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EVALUATION
APPLICATIONS
KEY REFERENCES
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NEED FOR NEW APPROACH:-
Oral route is the easiest and most convenient route for non
invasive administration.
Approximately 40% of new chemical drug moieties have poor
aqueous solubility and it is a major challenge to modern drug
delivery system.
To overcome these problems, various formulations strategies
are exploited including the use of surfactant, lipid permeation
enhancers, micronisation, salt formation, cyclodextrins,
nanoparticles and solid dispersions.
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Combination SURFACTANT
CO-
SURFACTANT
DRUG
OILS
Defined as isotropic mixtures of natural or synthetic oils, solid
or liquid surfactants and co-solvents/surfactants.
SEDDSs emulsify spontaneously to produce fine oil in- water
emulsions when introduced into an aqueous phase under gentle
agitation and spread readily in the gastro intestinal tract.
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xxxxx
SEDDSs typically produce emulsions with a droplet size
between 100–300 nm while self-micro-emulsifying drug
delivery systems (SMEDDSs) form transparent micro
emulsions with a droplet size of less than 50 nm
40% of New Drug Candidates show poor aqueous solubility
and thus poor bioavailability.
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ADVANTAGES:-
Quick Onset of Action.
Reduction in the Drug Dose.
Ease of Manufacture & Scale-up.
 Improvement in oral bioavailability.
Inter-subject and Intra-subject variability and food effects.
No influence of lipid digestion process.
Increased drug loading capacity.
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DISADVANTAGES:-
Lack of good in vitro models for assessment of the
formulations for SEDDS.
The traditional dissolution methods does not work, because
these formulations potentially are dependent on digestion prior
to release of the drug.
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COMPOSITION OF SEDDS:-
1.DRUG
The drugs with poor aqueous solubility and high permeability
are classified as class II drug by Biopharmaceutical classification
system (BCS). These drugs are use to formulate SEDDS.
Class IV
Low Solubility
Low
Permeability
Class I
High Solubility
High
Permeability
Class III
High Solubility
Low
Permeability
Class II
Low Solubility
High
Permeability
P
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y Solubility4/15/2015 9SEDDS

2. OIL
Oils are the most important excipient.
Help in solubilizing the lipophilic drug in a high amount.
Facilitate self-emulsification and increase the fraction of
lipophilic drug transported.
Increase absorption from the GI tract.
Both long-chain triglyceride and medium-chain triglyceride oils
with different degrees of saturation have been used for the
formulation of SEDDSs.
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Excipient name
(commercial name)
Examples of commercial products
in which it has been used
Corn oil Sandimmune soft gelatin capsule,
Depakene capsule
Olive oil Sandimmune oral solution
Oleic acid Ritonavir soft gelatin capsule,
Norvir soft gelatin capsule
Sesame oil Marinol soft gelatin capsule
Hydrogenated soybean
oil
Accutane soft gelatin capsule,
Vesanoid soft gelatin capsule
DL-α-Tocopherol Neoral oral solution, Fortovase soft
gelatin capsule
Beeswax Vesanoid soft gelatin capsule
Peanut oil Prometrium soft gelatin capsule
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3. SURFACTANTS:-
Natural surfactants have limited ability to emulsify.
Non ionic surfactants are less toxic when compared to ionic
surfactants.
The usual surfactant strength ranges between 30–60% w/w of
the formulation in order to form a stable SEDDS.
Non-ionic surfactants with high hydrophilic–lipophilic balance
(HLB) values are used in formulation of SEDDS.
Surfactants are amphiphilic in nature and they can dissolve or
solubilize relatively high amounts of hydrophobic drug
compounds
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Excipient name
( commercial name)
Examples of commercial
products in which it has been
used
Polysorbate 20 (Tween 20) Targretin soft gelatin capsule
Polysorbate 80 (Tween 80) Gengraf hard gelatin capsule
Sorbitan monooleate (Span
80)
Gengraf hard gelatin capsule
Polyoxyl-35-castor oil
(Cremophor EL)
Gengraf hard gelatin capsule,
Ritonavir soft gelatin capsule
Polyoxyethylated glycerides
(Labrafil M 2125Cs)
Sandimmune soft gelatin
capsules
D-α-Tocopheryl polyethylene
glycol 1000 succinate (TPGS)
Agenerase soft gelatin capsule,
Agenerase
oral solution
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4. COSOLVENTS/ COSURFACTANTS-
Cosolvents may help to dissolve large amounts of hydrophilic
surfactants or the hydrophobic drug in the lipid base.
These solvents sometimes play the role as co-surfactant in the
microemulsion systems.
Alcohol is not included in SEDDS/SMEDDS due to it’s
migration.
Drug release is increased with increasing concentration of
cosurfactant in formulation.
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Excipient name
( commercial name)
Examples of commercial
products in which it has been
used
Ethanol Neoral soft gelatin capsule, Neoral
oral solution, Gengraf hard gelatin
capsule, Sandimmune soft gelatin
capsule.
Glycerin Neoral soft gelatin capsule,
Sandimmune soft gelatin capsule
Propylene glycol Neoral soft gelatin capsule, Neoral
oral solution, Lamprene soft
gelatin capsule.
Polyethylene glycol Targretin soft gelatin capsule,
Gengraf hard gelatin capsule,
Agenerase soft gelatin capsule.
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TERNARYPHASEDIAGRAM
Pseudo ternary phase diagram is used to map the for three
key excipients according to the resulting droplet size
following self emulsification, stability upon dilution and
viscosity.
 A Titration method is employed to construct phase diagram.
 Mixture of oil with surfactant is prepared at different ratios
(e.g. 10:0, 9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9, 0:10) into
different vials.
 A small amount of water in 5 % (w /w) increments is added
into the vials.
 Following each water addition the mixture in vials is
centrifuged for 2 to 3 minute and is incubated at 25 C or 48
hrs with gentle shaking.
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CONSTRUCTIONOF PHASE DIAGRAM
•The resulting mixture is evaluated by visual and microscopy
observation. For phase diagram the micro emulsion is the
region of clear and isotropic solution.
•Coarse emulsion is the region of cloudy dispersion.
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MECHANISM OF SELF EMULSIFICATION-
Self-emulsification takes place when the entropy change
favouring dispersion is greater than the energy required to
increase the surface area of the dispersion.
 The free energy of a conventional emulsion formulation is a
direct function of the energy required to create a new surface
between the oil and water phases.
 The two phases of the emulsion tend to separate with time to
reduce the interfacial area and thus the free energy of the
systems.
 Free energy in the micro-emulsion formation is directly
proportional to the energy required to create new surface
between the two phases, and is given by the equation-
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SEDDS

Where,
ΔG=Free energy associated with the process.
N=No. of droplets of radius r.
σ=Represents interfacial energy.
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PREPARATIONOF SEDDS:-
A) SOLIDIFICATION TECHNIQUES FORTRANSFORMING
LIQUID/SEMISOLID:
Capsule filling with liquid and semisolid self-
emulsifying formulations:
Capsule filling is the simplest and the most common technology
for the encapsulation of liquid or semisolid SE formulations for
the oral route.
four-step process:
A)Heating of the semisolid excipient to at least 20˚C above its
melting point.
B) Incorporation of the active substances (with stirring).
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SEDDS

C) Capsule filling with the molt cooling to room temperature.
For liquid formulations, it involves a two-step process.
D) Filling of the formulation into the capsules followed by
sealing of the body and cap of the capsule, either by banding or
by micro spray sealing.
B) SPRAY DRYING:-
Technique involves the preparation of a formulation by mixing
lipids, surfactants, drug, solid carriers, and solubilization of the
mixture before spray drying.
The solubilized liquid formulation is then atomized into a spray
of droplets.
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The droplets are introduced into a drying chamber, where the
volatile phase (e.g. the water contained in an emulsion)
evaporates, forming dry particles under controlled temperature
and airflow conditions.
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C) MELTGRANULATION
Melt granulation is a process in which powder agglomeration
is obtained through the addition of a binder that melts or
softens at relatively low temperatures.
D) MELT EXTRUSION SPHERONIZATION
Melt extrusion is a solvent-free process that allows high drug
loading (60%), as well as content uniformity.
Extrusion is a procedure of product of uniform shape and
density, by forcing it through a die under controlled
temperature, product flow, and pressure conditions.
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(1)ORAL DELIVERY
(A) SELF EMULSIFYING CAPSULE
Poor water soluble drugs can be dissolved in SEDDS and
encapsulated in hard or soft gelatin capsules to produce
convenient single unit dosage forms.
Administration of capsules containing conventional liquid SE
formulations, micro emulsion droplets form and subsequently
disperse in the GI tract to reach sites of absorption.
If irreversible phase separation of microemulsion occurs an
improvement of drugs absorption can’t be expected.
 For handling this problem, sodium dodecyl sulfate was added
into the SE formulation.
DOSAGE FORMSOF SEDDS:-
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(B) SELF--EMULSIFYING SUSTAINED /
CONTROLLED RELEASE:
Combination of lipids and surfactant has presented great
potential preparing SE tablets.
SE tablets are of great utility in obviating adverse effect.
 Inclusion of indomethacin (or other hydrophobic NSAID)
for example, into SE tablets may increase its penetration
efficacy through GI mucosal membrane, potentially reducing
GI bleeding
(C) SELF EMULSIFYING SUSTAINED /
CONTROLLED RELEASE PELLETS:
Pellets, as a multiple unit dosage form, possess many advantages
over conventional solid dosage form, such as
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Flexibility of manufacture, reducing intra subject and inter
subject variability of plasma profile and minimizing GI
irritation without lowering drug bioavailability.
(D) SELF EMULSIFYING SOLID DISPERSIONS:
Solid dispersions could increase the dissolution rate and
bioavailability of poorly water soluble drugs but still some
manufacturing difficulties and stability problems existed.
(2) TOPICAL DELIVERY:
Topical administration of drugs can have advantages over other
methods for several reasons, one of which is the avoidance of
hepatic first pass metabolism of the drugs and related toxicity
effects.
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(3) OCULARS AND PULMONARY DELIVERY:
For the treatment of eye disease, drugs are essentially delivered
topically o/w microemulsion have been investigated for ocular
administration, to dissolve poorly soluble drugs, to increase
absorption and to attain prolong release profile.
(4) PARENTERAL DELIVERY:
Parenteral administration of drugs with limited solubility is a
major problem in industry because of the extremely low
amount of drug actually delivered as target site.
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EVALUATION OF SEEDS:-
1. Thermodynamic Stability Studies
2. Dispersibility test
3. Turbidimetric Evaluation
4. Viscosity Determination
5. Droplet Size Analysis and Particle Size
Measurements
6. Refractive Index and Percent Transmittance
7. Electro Conductivity Study
8. In vitro Diffusion Study
9. Drug Content
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THERMODYNAMIC STABILITY STUDIES
Heating cooling cycle
•Six cycles between refrigerator temperature 4⁰C and 45⁰C
with storage at each temperature of not less than 48 h is
studied.
•Those formulations, which are stable at these temperatures,
are subjected to centrifugation test.
Centrifugation
•Passed formulations are centrifuged at room temperature at
3500 rpm for 30 min.
•Those formulations that does not show any phase separation are
taken for the freeze thaw stress test.
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Freeze thaw cycle:-
Freeze was employed to evaluate the stability of formulation.
Thermodynamic stability was evaluated at difference temp. To
check the effect of temp. the formulation was subjected to freeze
thaw cycle(-20ºC) for 2-3 days.
Those formulations passed this test showed good stability with
no phase separation, creaming, or cracking.
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DISPERSIBILITYTEST:-
The efficiency of self-emulsification of oral nano or micro
emulsion is evaluated by using a standard USP XXII dissolution
apparatus for dispersibility test.
Solution Tested: 1ml
Medium: 500 ml water
Temperature: 37 ± 1 ⁰C.
Paddle speed : 50 rpm
Grade A: Rapidly forming (within 1 min) nano-emulsion, having
a clear or bluish appearance.
Grade B : Rapidly forming slightly less clear emulsion having a
bluish white appearance.
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SEDDS

Grade C: Fine milky emulsion that 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 recommended for SEDDS formulation.
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TURBIDIMETRIC EVALUATION:-
Nepheloturbidimetric evaluation is done to monitor the
growth of emulsification.
Fixed quantity of Self emulsifying system is added to fixed
quantity of suitable medium (0.1N hydrochloric acid) under
continuous stirring (50 rpm) on magnetic hot plate at
appropriate temperature, and the increase in turbidity is
measured, by using a turbidimeter.
However, since the time required for complete emulsification
is too short, it is not possible to monitor the rate of change of
turbidity (rate of emulsification)
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VISCOSITY DETERMINATION:-
o The SEDDS system is generally administered in soft gelatin or
hard gelatin capsules. So, it should be easily pourable into
capsules and such systems should not be too thick.
oThe rheological properties of the micro emulsion are evaluated
by Brookfield viscometer.
oThe viscosities determination conform whether the system is
w/o or o/w.
oIf the system has low viscosity then it is o/w type of the system
If the system has high viscosity then it is w/o type of the system
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DROPLETSIZE ANALYSIS:-
The droplet size of the emulsions is determined by photon
correlation spectroscopy (which analyses the fluctuations in
light scattering due to Brownian motion of the particles) using a
Zetasizer able to measure sizes between 10 and 5000 nm.
REFRACTIVE INDEX AND PERCENT TRANSMITTANCE:-
Refractive index and percent transmittance prove the
transparency of formulation.
The refractive index of the system is measured by refractometer
by putting a drop of solution on slide and comparing it with
water (1.333).
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The percent transmittance of the system is measured at
particular wavelength using UV spectrophotometer by using
distilled water as blank.
If refractive index of system is similar to the refractive index of
water (1.333) and formulation have percent transmittance > 99
percent, then formulation have transparent nature.
ELECTRO CONDUCTIVITY STUDY:-
The SEDD system contains ionic or non-ionic surfactant, oil,
and water.
This test is performed for measurement of the electro
conductive nature of system.
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The electro conductivity of resultant system is measured by
electro conductometer.
In conventional SEDDSs, the charge on an oil droplet is
negative due to presence of free fatty acids.
IN VITRO DIFFUSION STUDY:-
In vitro diffusion studies are carried out to study the drug release
behavior of formulation from liquid crystalline phase around the
droplet using dialysis technique.
DRUGCONTENT:-
Drug from pre-weighed SEDDS is extracted by dissolving in
suitable solvent. Drug content in the solvent extract was
analyzed by suitable analytical method against the standard
solvent solution of drug.
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APPLICATION
Improvement in Solubility and bioavailability:
Protection against Biodegradation:
Controlling the release of
drug:
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KEY REFERENCES
Nigade P.M., Patil S. I., Tiwari S.S. (2012). “Self
Emulsifying Drug Delivery System (SEDDS)”: A Review.
IJPBS. 2(2), 42-52.
 Sarpal K., Pawar Y. B., and . Bansal A.K .(2010)”Self
Emulsifying Drug Delivery System (SEDDS) A Strategy To
Improve Oral Bioavailability”, (CRIPS). 11(3), 42-49.
 Mistry R .B., Sheth N .S.,(2011) A review: “Self Emulsifying
Drug Delivery System”. IJPPS. 3(2), 23-28
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Mahapatra A K., Murthy P N., Swadeep B, Swain R P.(2014).
”Self-Emulsifying Drug Delivery Systems (SEDDS): An
Update from Formulation Development to Therapeutic
Strategies”. IJPTR 6(2), 546-568
Taksande J. B., Trivedi R., Mahore J. G., Wadher K J.(2011)
“Self-Emulsifying Drug Delivery System: Hitherto and Resent
advances”. IJRAP 2011, 2(4) 1087-1095
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SEDDS

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