Upon contact with G.I environment the product becomes self emulsified

1. 1
SELF EMULSIFYING DRUG DELIVERY
SYSTEM
24/07/2018 SAI BHARGAV.N
NARISEPALLI SAI BHARGAV
(17L81S0309)
A Seminar Presented as a part of
I Year M. Pharm II Semester Curriculum
Department of Pharmaceutics
Raghavendra Institute of Pharmaceutical Education and Research
(RIPER)- Autonomous,
Ananthapuramu, Andhra pradesh -515721
JULY - 2018

2. CONTENTS
 Definition
 Mechanism
 Formulation aspects
 Preparation methods
 Evaluation parameters
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3. DEFINITION
 Self emulsifying drug delivery systems (SEDDS), which are isotropic
mixture of oils, surfactants, solvents and co-solvents/surfactants, which
emulsify spontaneously to produce fine oil-in water emulsions when
introduced into aqueous phase under gentle agitation
 SEDDS can be used for the design of formulations in order to improve the
oral absorption of highly lipophilic compounds.
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4. 4

5. ADVANTAGES
 Quick onset of action
 Reduction in the drug dose
 Ease of manufacture & scale up
 Improvement in oral bioavailability
 Reduce in Inter-subject and intra-subject variability
 Ability to deliver peptides that are prone to enzymatic hydrolysis in
GIT
 No influence of lipid digestion process
 Increased drug loading capacity
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7. Disadvantages :
 Traditional dissolution methods do not work, because these
formulations potentially dependent on digestion prior to release of the
drug
 In vitro model needs further development and further development and
validation before its strength can be evaluated
 Further development will be based on in vitro – in vivo correlations and
therefore different protype lipid based formulations needs to be
developed and tested in vivo in a suitable animal model
 Chemical instabilities of drugs and high surfactant concentrations in
formulations (30 - 60%)
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8. 8
MECHANISM

9.  The spontaneous formation of micro emulsion droplet was due to the
formation of a complex film at the oil-water interface by the
surfactant and co-surfactant
 Thermodynamic theory explains that emulsification occurs, when
the entropy changes that favors dispersion is greater than the energy
required to increase the surface area of the dispersion and the free
energy is negative
 The free energy in the micro emulsion is a direct function of the
energy required to create a new surface between the two phases and
can be described by
ϪG=Ʃ N Л 2 σ
 N=no of droplets with R=radius & σ =interfacial energy
 With time, the 2 phases of the emulsion tend to separate to reduce
the interfacial area, and subsequently the free energy of the system
decreases
 The emulsion resulting from aqueous dilution are stabilized by
conventional emulsifying agents, which forms a mono layer around
the emulsion droplets, and hence reduce the interfacial energy, as
well as providing a barrier to prevent coalaescence
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10. PROPERTIES
 They are able to self emulsify rapidly in G.I fluids & under the
influence of gentle agitation provided by peristalic and other
movements of G.I.T, they form a fine O/W emulsion
 They can effectively incorporate drug (hydro phobic or philic)
within the oil surfactant mixture
 They can be used for liquid as well as solid dosage forms
 They require lower dose of drug with respect to conventional dosage
forms
Drug properties :
 Dose should not be high
 Drug should be oil soluble
 High melting point drug is poorly suited to SEDDS
 Log P value should be high
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11. Important parameter for excipient to SEDDS :
 The solubility of drug in the formulation as such and upon dispersion
 The rate of digestion (for formulations susceptible to digestion)
 The solubility capacity of the digested formulation
Factors affecting:
 Nature of dose of drug
 Polarity of the lipophilic phase
Applications :
 Improvement in solubility and bioavailability
 Protection against biodegradation
 Controlling the release of drug
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13. 13
FORMULATION ASPECTS

14. 14

15. Formulation components :
 Drug
 Oil
 Surfactant
 Co-surfactant
 Co-solvent
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16. Oils :
 It will solubilize the required dose of the lipopholic drug or
facilitates the self emulsification process and also increase the
fraction of lipophilic drug transported via the intestinal lymphatic
system, thereby increasing absorption from GI tract depending on
the molecular nature of the triglyceride
 Modified or hydrolyzed vegetable oils are widely used
 E.g. Triglyceride, Hydrolyzed corn oil, Corn oil, Olive oil, Sesame
oil, Hydrogenated soyabean oil, Mixture of mono and di-glycerides
of caprylic acid medium chain mono and di-glycerides, Castor oil,
Cotton seed oil, Sunflower oil
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17. Surfactants :
 Surfactants which have high HLB values will assist the immediate
formation of O/W droplets & rapid spreading in aqueous media
 Non ionic surfactants are mostly preferred
 Surfactants used in formulations may increase the bioavailabilty by
various mechanisms like improving drug dissolution, increasing
intestinal epithelial permeability, increasing tight junction
permeability, decreased/inhibited pglycoprotein drug efflux
E.g Anionic surfactants – potassium laurate, SLS
Cationic surfactants – quaternary ammonium halide
Ampholytic surfactant – sulfobetaines
Non ionic surfactants – spans, tweens
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18. Co-solvent :
 The concentration of surfactant can be reduced by the use of co-
surfactants
 Role- to lower the interfacial tension to a very small even transient
negative value, at this value the interface would expand to form fine
dispersed droplets
 E.g – ethanol, poly ethylene glycol, propylene glycol
Co-surfactant :
 Generally agent with 10-14 HLB was used
 Preference given to alcohols of intermediate chain length such as
hexanol, pentanol, octanol which were known to reduce the oil water
interface and allow spontaneous formation of micro emulsion
 E.g – span, cayrol 90, capmul
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19. STEPS INVOLVED IN SEDDS PREPARATION
Step 1 :
 Screening of excipients and solubility studies
Step 2 :
 To find out correct combination (pseudo ternary phase diagram)
Step 3:
 Addition of drug
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20. PREPARTION METHODS
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21. SPRAY DRYING
Oil+ surfactant+ drug+ solid carrier
spray
Drying chamber through nozzle
evaporate
Volatile vehicles leaving behind solid particles
compress
Tablets, or filled into capsules
Ex: nimodipine self microemulsifying formulation by using dextran as carrier
this is also applied for developing of curcumin & dexibuprofen
this technique used to prepare dry emulsion by removing water from an
ordinary emulsion
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22. SPRAY COOLING
Molten formulation
spray
Cooling chamber
Molten mixture contact with the cooling air
congeal & recrystallize
Spherical solid particles
collects into bottom
As fine powder
Development of solid forms such as capsules, tablets
Ex: Poly oxyl glycerides
Drugs: Praziquantel, Diclofenac
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23. MELT EXTRUSION
 Based on the property of materials which can be easily extruded and
spheronized
 These do not require liquid excipients although constant temperature
and pressure has to be maintained to achieve drug loading
 In extrusion raw material with plastic properties are converted into
uniform pellets of varying size which depend on size of extruder
aperture
 It ensures content uniformity and widely used in preparation of
pellets and granules
 Ex: SNE formulation of ubiquinone
 Propranalol and Diazepam (SE pellets & bilayerd cohesive SE
pellets)
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24. TYPES OF S-SEDDS.
CAPSULES
TABLETS
PELLETS
POWDERS IMPLANTS
SOLID
DISPERSIONS
SOLID SELF-EMULSIFYING DOSAGE
FORMS.
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25. DIFFERENCE BETWEEN SEDDS AND
SMEDDS.
1. HIGHER SURFACTANT AND CO-
SURFACTANT /OIL RATIO:-
SEDDS SMEDDS
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EVALUATION PARAMETERS

27.  Dispersibility test
 Rheological properties determination
 Thermodynamic stability studies
 Robustness to dilution
 Turbidimetric evaluation
 Droplet size & particle size measurements
 Self emulsification time
 Zeta potential determination
 Invitro diffusion study
 Invitro dissolution technique
 Liquefaction time
 Refractive index & % transmittance
 Permeation studies
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28. Dispersibility test :
 The efficiency of self-emulsification of oral nano or micro emulsion
is evaluated by using a standard USP II dissolution apparatus for
dispersibility test
 Solution tested : 1 ml
 Medium : 500 ml water
 Temperature : 37
 Paddle speed : 50 rpm
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29.  Grade A : rapidly forming (within 1 min) nanoemulsion having a clear
or blush appearance
 Grade B : rapidly forming slightly less clear emulsion having a bluish
white appearance
 Grade C : fine milky emulsion that formed within 2 minutes
 Grade D : dull grayish white emulsion having slighty oil 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 & B formulations will remain as nanoemulsion when dispersed
in GIT while formulation falling in Grade C could be recommonded for
SEDDS formulation 29

30. Viscosity determination:
The SEDDS system is generally administered in soft gelatin or hard
gelatin capsules so it can be easily pourable into capsules and such system
should not too thick to create a problem the rheological properties of the
micro emulsion are measured by Brookefield viscometer
The viscosity determination confirms whether the system is
O/W or W/O if system is low viscosity then it is O/W type of the system
and vice versa
Droplet size analysis:
The Droplet size of the emulsion is determined by photon correlation
spectroscopy ( which analyses the fluctuations in light scattering due to
Brownian motion of the particles) using a zeta sizer able to measure size
between 10 – 500 nm
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31. Thermodynamic studies :
 The physical stability of a lipid based formulation is also crucial to
its performance, which can be adversely affected by precipitation of
the drug in the excipient matrix
 In addition poor formulation physical stability can lead to phase
separation of the excipient affecting not only formulation
performance but visual appearance as well
 In addition incompatabilities between the formulation and the gelatin
capsules shell can lead to brittleness or deformation delayed
disintegration or incomplete release of drug
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32. Heating cooling cycle:
 Six cycles between refrigerator temperature 4 C and 45 C 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 tests
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
Freeze thaw cycle :
 It was employed to evaluate the stability of formulation
 Thermodynamic stability was evaluated at different temperatures to
choke the effect of temperature the formulation was subjected to
freeze thaw cycle (-20C) for 2-3 days
 Formulations are exposed to atleast 3 freeze thaw cycles
 Those formulations passed this test showed good stability with no
phase separation creaming or cracking
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33. Turbidimetric evaluation:
 Nephloroturbidimetric evaluation is done to monitor th egrpwth 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 temperature 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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34. Electro conductivity study :
 The SEDDS contains ionic or non-ionic surfactant oil and water
 This test is performed for measurement of the electro conductive nature of the
system
 This is measured by electro conductometer
Invitro Diffusion study :
 In vitro diffusion studies are carried out to study the drug release behaviour of
formulation from liquid crystalline phase around the droplet using dialysis
technique
Drug content :
 Drug from preweighed 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 34

35. M
DRUG. TRADE NAME/
COMPANY.
TYPE OF
FORMULATION
.
INDICATION.
Cyclosporin A Neoral,Sandimmune
(Novartis)
Soft gelatin capsule Immuno-
suppressant
Ritonavir Norvir(Abbott) Soft gelatin capsule HIV Antiviral
Sanquinavir Fortovase(Roche) Soft gelatin capsule HIV Antiviral
Valproic acid Convulex (Pharmacia) Soft gelatin capsule Anti-epileptic
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36. References :
 Priya thakare, Vrushali mogal, Pankaj, Jaydeep, Sanjay, a review on self-
emulsified drug delivery system, Pharmaceutical and biological
evaluations, April 2016, vol 3, Issue 2: 140-153, ISSN 2394-0859
 Pallavi M etal., Self emulsifying drug delivery system: A review,
International journal of pharmacy and biological sciences, April 2012,
volume 2, Issue 2: 42-52, eISSN: 2230-7605
 Hamed etal., Self emulsifying drug delivery system : A review,
International journal of pharmaceutical and chemical sciences, June
2013, Volume 2, Issue 1:34-44, ISSN: 2277-5005
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