SEEDS- SELF EMULSIFYING DRUG DELIVERY SYSTEMS

SELF-
EMULSIFYING
DRUG DELIVERY
SYSTEMS(SEDDS)
Pharmaceutics
PRESENTED BY:
U SIVA PRASAD
B.PHARMACY

Topics for discussion
Core Concepts
INTRODUCTION
DEFINITION AND ADVANTAGES
COMPOSITION OF SEDDS
MECHANISM OF SELF EMULSIFICATION
FORMULATION APPROACH
IN-VITRO EVALUATION OF SEDDS
SEDDS VS SMEDDS
RECENT APPROACHES
MARKETED PRODUCTS
CONCLUSION
REFERENCES
SEDDS | 118071 | SVCP

Oral route is the easiest and most convenient route for non-
invasive administration.
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.
INTRODUCTION

DEFINITION
SEDDS or self-emulsifying oil formulations (SEOP) are 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 gastrointestinal tract.
SEDDS 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.

Advantages
Enhanced oral bioavailability enabling a
reduction in dose
Protection of sensitive drug substances.
More consistent drug absorption.
Selective targeting of drugs toward
specific absorption window in GIT
Protection of drug(s) from the gut
environment.
Control of the delivery profile
Reduced variability including food effects
High drug loading efficiency.
These dosage forms reduce the gastric
irritation produced by drugs.

Drawbacks
Lack of good in-vitro models for
assessment of the formulations for
SEDDS.
The traditional dissolution methods
don't work, because these formulations
potentially are dependent on digestion
prior to the release of the drug.
Large Quantities of Surfactants in Self
Emulsifying Formulations irritates GIT.
Volatile Co- solvents can migrate on
capsule shells.

CLASSIFICATION OF LIPID
FORMULATIONS SYSTEMS

Why we need SEDDS?

Composition
of SEDDS
Drug (API)
Oils
Surfactants
Co- Surfactants

DRUG (API)
The Drugs with poor aqueous solubility
and high permeability are classified as
Class II Drugs by Biopharmaceutical
Classification System (BCS). These drugs
are used to formulate SEDDS.
E.g. of BCS Class II Drugs :
Acetylsalicylic Acid, Ibuprofen,
Captopril, Ibrutinib etc.

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 TG's and medium-chain TG
oils with different degrees of saturation have
been used for the formulation of SEDDSs.
OIL

LIST OF OILS USED IN SEDDS
DL-alpha-Tocopherol
Fractionated triglyceride of coconut oil(medium-chain triglyceride)
Fractionated triglyceride of palm seed oil(medium-chain triglyceride)
A mixture of mono-and di-glycerides of caprylic/capric acid
Corn oil mono,di,tri-glycerides
Medium-chain mono-and di-glycerides
Corn oil, Olive oil
Oleic acid
Sesame oil
Hydrogenated soyabean oil & vegetable oils
Soyabean oil, Peanut oil
Beeswax SEDDS | 118071 | SVCP

Natural surfactants have a 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 the formulation of
SEDDS.
Surfactants are amphiphilic in nature and can dissolve or
solubilize relatively high amounts of hydrophobic drug
compounds
SURFACTANTS
Improve Drug Dissolution
Increase Intestinal
epithelial permeability.
Increased tight junction
permeability.
Mechanisms:
1.
2.
3.

List of Surfactants used in SEDDS
Polysorbate 20 (Tween 20)
Polysorbate 80 (Tween 80)
Sorbitan monooleate (Span80)
Polyoxy-35-castor oil(Cremophor RH40)
Polyoxy-40-hydrogenated castor oil (Cremophor RH40)
Polyoxyethylated glycerides (Labrafil M 2125Cs)
Polyoxyethlated oleic glycerides (Labrafil M1944Cs)
D-alpha Tocopheryl polyethylene glycol 1000 succinate (TPGS)

Co-solvent/Co-
Surfactant
Cosolvents may help to dissolve large
amounts of hydrophilic surfactants or the
hydrophobic drug in the lipid base.
These solvents sometimes play the role of
co-surfactant in microemulsion systems.
Alcohol is not included in
SEDDS/SMEDDS due to its migration.
Drug release is increased with increasing
concentration of cosurfactant in the
formulation.

The free energy of a conventional emulsion formation is a direct
function of the energy required to create a new surface between
the two phases and can be described by equation
Where G is the free energy associated with the process (ignoring
the free energy of mixing), N is the number of droplets of radius,
r, and σ represents the interfacial energy.
With time, the two phases of the emulsion will tend to separate, in
order to reduce the interfacial area, and subsequently, the free energy
of the systems.
MECHANISM OF ACTION

MECHANISM OF ACTION

GENERAL FORMULATION
APPROACHES
Preliminary solubility profiling studies are performed for the
selection of oil.
Drug excipient compatibility studies.
Preparation of a series of SEDDS system containing drug in
various oil and surfactant with different combinations.
Optimization of formulation on the basis of in-vitro self-
emulsification properties, droplet size analysis, stability
studies, robustness to dilution upon addition to water under
mild agitation conditions.

DOSAGE
FORM OF
SEDDS
Oral Delivery:
Self- Emulsifying capsule.
Self- Emulsifying sustained/ controlled release tablet.
Self- Emulsifying sustained/ controlled release
pellets.
Self- Emulsifying solid dispersions.
Topical Delivery.
Oculars and pulmonary delivery.
Parenteral Delivery.
1.
2.
3.
4.

METHODS OF SOLIDIFICATION
Capsule filling with liquid and semi-solid
self-emulsifying formulations.
Spray drying.
Spray cooling
Adsorption to solid carriers.
Melt Granulation.
Melt Extrusion Spheronization.
1.
2.
3.
4.
5.
6.

Droplet size analysis and zeta potential measurements
Viscosity determination
In vitro diffusion studies
Thermodynamic stability studies
Dispersibility test
Drug content analysis
Turbidimetric evaluation
Refractive index and percent transmittance
Electroconductivity studies
1. Centrifugation
2. Freeze-Thaw Cycle
3. Heating Cooling Cycle
EVALUATION OF SEDDS

Droplet size analysis and zeta
potential measurements
Droplet size and zeta potential are
measured by Zeta sizer
3000 HAS (Malvern Instruments, UK) able to
measure size between 10 to 3000nm

Viscosity Determination
The rheological properties of
microemulsions are evaluated by
Brookfield Viscometer.
The viscosities determination confirms
whether a system is W/O or O/W.
If a system has low viscosity then it is the
O/W type of the system, if high viscosities
then it is the W/O type of system.

In-vitro diffusion studies
This test is carried out by dialysis technique.
Drug is placed in dialysis tube which is
kept in USP dissolution apparatus II containing
900ml of dialysis medium at 37°C and stirred at
100 rpm.

Dispersibility Test
The efficiency of self-emulsification of oral nano or microemulsion
is assessed by using a standard USP XXII dissolution apparatus 2
for dispersibility test. One milliliter of each formulation was added
in 500 mL of water at 37 ± 1 °C at 50 rpm. It passes the test.
If it is rapidly forming (within 1 min) nanoemulsion, having a clear
or bluish appearance. Or
If it is rapidly forming, slightly less clear emulsion, having a
bluish-white appearance. Or
If it is a fine milky emulsion that formed within 2 min.

Incompatibility between formulation and gelatin shell.
Delay Disintegration.
Incomplete Drug Release.
Heating Cooling Cycle
Centrifugation
Freeze Thaw Cycle
It includes the evaluation of the stability of the product includes the
phase separation
1.
2.
3.

Six cycles between refrigerator temperature 4°C and
45°C with storage at each temperature of not less
than 48 hr is studied.
Those formulations, which are stable at these
temperatures, are subjected to centrifugation test.
Heating Cooling Cycle:

Thermodynamic stability
studies
Passed formulations are centrifuged at room
temperature at 3500rpm for 30 min.
Those formulations that don't show any
phase separation are taken for the freeze-
thaw stress test.
Centrifugation :

The freeze was employed to evaluate the
stability of the formulation.
Thermodynamic stability was evaluated at
different temp. To check the effect of
temperature the formulation was subjected to a
freeze-thaw cycle (-20°C) for 2-3 days.
Freeze-thaw cycle:

The formulation is exposed to at least three
freeze-thaw cycles. Those formulations that
passed this test showed good stability with no
phase separation, creaming, or cracking.
Sup]pose it shows thermodynamically unstable
formulation which had larger droplet size
distribution upon dilution.
Freeze-thaw cycle:

Drug content Analysis:
It is measured by HPLC.
Electro Conductivity
Study:
The electroconductivity of the
resultant system is measured by an
electro conductometer.
In conventional SEDDSs, the charge
on an oil droplet is negative due to
the presence of free fatty acids.

Refractive Index and
Percent Transmittance
The refractive index of the system is
measured by a refractometer by putting a
drop of solution on the slide and it
comparing it with water (1.333).
The percent transmittance of the system is
measured at a particular wavelength using a
UV spectrophotometer.

Turbidimetric Evaluation
Nepheloturbidimetric evaluation is done to
monitor the growth of emulsification. A
fixed quantity of self-emulsifying system is
added to a fixed quantity of suitable
medium (0.1N hydrochloric acid) under
continuous stirring (50 rpm) on a magnetic
hot plate at the appropriate temperature,
and the increase in turbidity is measured
using Turbidimeter.

SEDDS
Vs
SMEDDS

RECENT
APPROACHES
IN SEDDS

CONCLUSION
SEDDSs is a promising approach for the formulation
of lipophilic drugs and to improve the oral
bioavailability of drugs with poor aqueous solubility.
As alternatives for conventional forms, liquid
SEDDS, S-SEDDS are superior offering reduced
production costs, simplified industrial manufacture,
and improved stability as well as better patient
compliance.
Most importantly, S-SEDDS are very flexible for
developing various solid dosage forms for oral and
parenteral administration
It appears that more drug products will be formulated
as SEDDS in the very near future and these aspects
are the major areas for future research into S-SEDDS.

REFERENCES
Kavita Sapra et al. Self Emulsifying Drug Delivery System: A Tool in Solubility
Enhancement of Poorly Soluble Drugs Indo Global Journal of Pharmaceutical Sciences,
2012; 2(3): 313-332.
Jamilur Reza, Self-emulsifying drug delivery systems: a review, International Journal of
Pharmaceutical and Life Science, 2013; Volume 2: 2305-0330.
Mrs. Maria Saifee et al. American Journal of Advanced Drug Delivery 2013; 1(3): 323-
340.
Sachan R1 et al. Self-Emulsifying Drug Delivery System A NoveL Approach for
enhancement of Bioavailability International Journal of PharmTech Research 2010; 2(3):
1738-1745.
Ajay Kumar et al. Self-emulsifying drug delivery system: Future aspect International
Journal of Pharmacy and Pharmaceutical Sciences 2010; 2(14): 7-13.
Paridhi Bhargava et al., Advance Research in Pharmaceuticals& Biologicals 2011; 1(1):
2250- 0744.
R. Sunitha et al. Review Article international journal of research pharmacy and chemistry,
2011; 1(4): 2231-2781.
1.
2.
3.
4.
5.
6.
7.

SEEDS- SELF EMULSIFYING DRUG DELIVERY SYSTEMS

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to SEEDS- SELF EMULSIFYING DRUG DELIVERY SYSTEMS

Similar to SEEDS- SELF EMULSIFYING DRUG DELIVERY SYSTEMS (20)

Recently uploaded

Recently uploaded (20)

SEEDS- SELF EMULSIFYING DRUG DELIVERY SYSTEMS