Oral route is the main route of drug administration in many diseases. Major problem in oral route of drug administration is bioavailability which mainly results from poor aqueous solubility. This leads to lack of dose uniformity and high intrasubject/intersubject variability. It is found that 40% of active substances are poorly water-soluble. Various technologies are developed to overcome this problem, like solid dispersion or complex formation. Much attention has been given to lipid-based formulation with particular emphasis on self-micro emulsifying drug delivery system to improve the oral bioavailability of lipophilic drugs. It requires small amount of dose and also drugs can be protected from hostile environment in gut. Self-micro emulsifying drug delivery systems are specialized form of delivery system in which drug is encapsulated in a lipid base with or without pharmaceutical acceptable surfactant.

1. SELFMICRO EMULSIFYING DRUG DELIVERY SYSTEM [SMEDDS]
Sagar Kishor savale
Department of Pharmaceutics, North Maharashtra University, college of R.C.Patel Institute of
Pharmaceutical Education and Research, Shirpur, Dist.Dhule, Maharashtra.
Email: avengersagar16@gmail.com
ABSTRACT- Oral route is the main route of drug
administration in many diseases. Major problem in oral route
of drug administration is bioavailability which mainly results
from poor aqueous solubility. This leads to lack of dose
uniformity and high intrasubject/intersubject variability. It is
found that 40% of active substances are poorly water-soluble.
Various technologies are developed to overcome this problem,
like solid dispersion or complex formation. Much attention
has been given to lipid-based formulation with particular
emphasis on self-micro emulsifying drug delivery system to
improve the oral bioavailability of lipophilic drugs. It requires
small amount of dose and also drugs can be protected from
hostile environment in gut. Self-micro emulsifying drug
delivery systems are specialized form of delivery system in
which drug is encapsulated in a lipid base with or without
pharmaceutical acceptable surfactant.
KEYWORDS - Self-microemulsifying drug delivery systems
(SMEDDSs), Lipophilic compound, Droplet Size, Oral
Bioavailability.
INTRODUCTION
Self micro emulsifying drug delivery system (SMEDDS) or
self-micro emulsifying oil formulation (SEOF) is defined as
isotropic mixture of oil and surfactants or alternatively one or
more hydrophilic solvents and co-solvents. Upon milagitation
Followed by dilution in aqueous media such as the
gastrointestinal (GI) fluid, these systems can form fine oil in
water (o/w) emulsions or micro emulsions [self-micro
emulsifying drug delivery systems (SMEDDS)].
Microemulsion can have characteristic properties such as a
low interfacial tension, large interfacial area and capacity to
solubilize both aqueous and oil-soluble compounds. They can
be known as Modern colloidal drug delivery system.
Generally, SMEDDS are administered either as liquid dosage
forms or filled in soft gelatine capsules. As they are bound to
several disadvantages like leakage from capsule,
incompatibility with the capsule shell, low stability etc, solid
intermediates of these liquid SMEDDS have been prepared in
order to overcome these problems.
the basic difference between ; 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.
ADVANTAGES OF SMEDDS
1. Enhanced oral bioavailability enabling reduction in Dose. 2.
More consistent temporal profiles of drug Absorption. 3.
Selective targeting of drug(s) towards specific absorption
window in GIT. 4. Protection of drug(s) from the hostile
environment in gut. 5. Reduced variability including food
effects. 6. Protection of sensitive drug substances. 7. Liquid or
solid dosage forms. 8. In SMEDDS, the lipid matrix interacts
readily with water, forming a fine particulate oil-in-water
(o/w) emulsion. The emulsion droplets will deliver the drug to
the gastrointestinal mucosa in the dissolved state readily
accessible for absorption. Therefore increase in AUC i.e.
bioavailability and C max is observed with many drugs when
presented in SMEDDS. 9. Fine oil droplets empty rapidly
from the stomach and promote wide distribution of drug
throughout the intestinal tract and thereby minimizing
irritation frequently encountered with extended contact of
drugs and gut wall. 10.Ease of manufacture and scale up is
one of the most important advantage that make SMEDDS
unique when compared to other drug delivery system like
solid dispersion, liposomes, nanoparticles etc. 11. SMEDDS
has potential to deliver peptides that are processed to
enzymatic hydrolysis in GIT. 12. When polymer is
incorporated in composition of SMEDDS it gives prolonged
release of medicament. Formulation is composed of lipids,
surfactants and co-solvents. The system has the ability to form
an oil-on-water emulsion when dispersed by an aqueous phase
under gentle agitation. SMEDDS present drugs in a small
droplet size and well-proportioned distribution and increase
the dissolution and permeability. Furthermore, because drugs
can be loaded in the inner phase and delivered to the
lymphatic system, can bypass first pass metabolism. Thus
SMEDDS protect drugs against hydrolysis by enzymes in the
GI tract and reduce the presystolic clearance in the GI mucosa
and hepatic first-pass metabolism.
DRAWBACKS OF SMEDDS:
Lack of good predicative in vitro models for assessment of the
formulation is the most important problem in the development
of SMEDDS and other lipid-based formulation. These
formulations are dependent on digestion prior to release of the
drug so traditional dissolution method do not work. To mimic
this, in vitro model simulating the digestive processes of the
duodenum has been developed. This in vitro model needs

2. further development and validation before its strength can be
evaluated. Further development will be based on in vitro, in
vivo correlations and therefore different prototype lipid based
formulations need to be developed and tested in vivo in a
suitable animal model.
COMPOSITION
1) Oil
2) Surfactant
3) Co solvent / Co surfactant
4) Others components
OILS
The oil represents the most important excipient in the
SMEDDS formulation. Indeed it can solubilize relevant
amount of the poorly water soluble drug. Both long-chain
triglyceride (LCT) and medium chain triglyceride (MCT) oils
with different degrees of saturation have been used in the
design of SMEDD.
E.g. - Corn oil, olive oil, soybean oil, hydrolysed corn
Oil.
SURFACTANT
Surfactant molecules may be classified based
On the nature of the hydrophilic group within the
Molecule. The four main groups of surfactants are defined as
follows,
1 Anionic surfactants
2 Cationic surfactants
3 Ampholytic surfactants
4 Non-ionic surfactants
1: Anionic Surfactants, where the hydrophilic group carries a
negative charge such as carboxyl (RCOO-), sulphonate
(RSO3-) or sulphate (ROSO3-). Examples: Potassium laurate,
sodium lauryl sulphate.
2: Cationic surfactants, where the hydrophilic group carries a
positive charge. Example: quaternary ammonium halide.
3: Ampholytic surfactants (also called zwitterionic
surfactants) contain both a negative and a positive charge.
Example: sulfobetaines.
4: Non-ionic surfactants, where the hydrophilic group carries
no charge but derives its water solubility from highly polar
groups such as hydroxyl or polyoxyethylene (OCH2CH2O).
Examples: Sorbitan esters (Spans), polysorbates
(Tweens).
Non-ionic surfactants with high hydrophiliclipophilic
Balance (HLB) values are used in formulation of SMEDDS.
The usual surfactant strength ranges between 30-60% w/w of
the formulation in order to form a stable SMEDDS.
Surfactants having a high HLB and hydrophilicity assist the
immediate formation of o/w droplets and/or rapid spreading of
the formulation in the aqueous media. Surfactants are
amphiphilic in nature and they can dissolve or solubilize
relatively high amount of hydrophobic drug compounds.
COSOLVENTS
Organic solvents such as ethanol, propylene glycol (PG) and
polyethylene glycol (PEG) are suitable for oral delivery and
they enable the dissolution of large quantities of either the
hydrophilic surfactant or the drug in the lipid base. These
solvents can even act as co surfactants in micro emulsion
systems. Alternately alcohols and other volatile cosolvents
have the disadvantage of evaporating into the shells of the soft
gelatin or hard sealed gelatin capsules in conventional
SMEDDS leading to drug precipitation.
Co-surfactant
Most single-chain surfactants do not lower the oil-water
interfacial tension sufficiently to form microemulsion nor are
they of the correct molecular structure. Further under certain
condition, a combination of oil, water and surfactant will
result in a phase where there are orderly planes of oil and
water separated by monomolecular layer of surfactant. This
type of phase is known as liquid crystal (lamellar phase).
Liquid crystals formation can be detected by large increase in
viscosity. Co-surfactant is added to further lower the
interfacial tension between the oil and water phase, fluidize
the hydrocarbon region of the interfacial-film, and to
influence the film curvature. Typical co-surfactants are short
chain alcohols (ethanol to butanol), glycols such as propylene
glycol, medium chain alcohols, amines or acids. Abe et al
(1986) concludes that the role of co-surfactant is to destroy
liquid crystalline or gel structures that form in place of a
microemulsion phase. They also conclude that Cosurfactant
free microemulsion in most system cannot be made except at
high temperature. El-Nokaly et al summarized the role of a
Co-surfactant as following: -
1) Increase the fluidity of the interface
2) Destroy liquid crystalline or gel structure which would
Prevent the formation of microemulsion.
3) Adjust HLB value and spontaneous curvature of the
Interface by changing surfactant partitioning characteristic.
FORMULATION
With a large variety of liquid or waxy excipients available,
ranging from oils through biological lipids, hydrophobic and
hydrophilic surfactants, to water-soluble co-solvents, there are
many different combinations that could be formulated for
encapsulation in hard or soft gelatin or mixtures which
disperse to give fine colloidal emulsions.
The following should be considered in the formulation of a
SMEDDS
• The solubility of the drug in different oil, surfactants and co
solvents.

3. • The selection of oil, surfactant and co solvent based on the
solubility of the drug and the preparation of the phase
diagram.
• The preparation of SEDDS formulation by dissolving the
drug in a mixture of oil, surfactant and co-solvent
[18]
.
The addition of a drug to a SMEDDS is critical because the
drug interferes with the self-microemulsification process to a
certain extent, which leads to a change in the optimal oil-
surfactant ratio. So, the design of an optimal SMEDDS
requires preformulation-solubility and phase-diagram studies.
In the case of prolonged SMEDDS, formulation is made by
adding the polymer or gelling agent.
MECHANISM OF SELF – EMULSIFICATION
The process by which self-emulsification takes place is not yet
well understood. However, according to Reiss, self-
emulsification occurs when the entropy change that favors
dispersion is greater than the energy required to increase the
surface area of the dispersion. In addition, 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 s 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. Therefore, the
emulsions resulting from aqueous dilution are stabilized by
conventional emulsifying agents, which form a monolayer
around the emulsion droplets, and hence, reduce the interfacial
energy, as well as providing a barrier to coalescence. In the
case of self-emulsifying systems, the free energy required to
form the emulsion is either very low and positive, or negative
(then, the emulsification process occurs spontaneously).
Emulsification requiring very little input energy involves
destabilization through contraction of local interfacial regions.
For emulsification to occur, it is necessary for the interfacial
structure to have no resistance to surface shearing. In earlier
work, it was suggested that the ease of emulsification could be
associated with the ease by which water penetrates into the
various LC or gel phases formed on the surface of the droplet.
According to Wakerly et al. the addition of a binary mixture
(oil/non-ionic surfactant) to water results in interface
formation between the oil and aqueous-continuous phases,
followed by the solubilisation of water within the oil phase
owing to aqueous penetration through the interface. This will
occur until the solubilisation limit is reached close to the
interface. Further aqueous penetration will result in the
formation of the dispersed LC phase. As the aqueous
penetration proceeds, eventually all material close to the
interface will be LC, the actual amount depending on the
surfactant concentration in the binary mixture. Once
formed, rapid penetration of water into the aqueous cores,
aided by the gentle agitation of the self-emulsification
process, causes interface disruption and droplet
formation. The high stability of these self-emulsified
systems to coalescence is considered to be due to the LC
interface surrounding the oil droplets. The involvement of
the LC phase in the emulsion formation process was
extensively studied by Pouton et al. Later, Craig et al. used
the combination of particle size analysis and low
frequency dielectric spectroscopy (LFDS) to examine the
self-emulsifying properties of a series of Imwitor 742 (a
mixture of mono- and diglycerides of capric and caprylic
acids)/Tween 80 systems
.
The dielectric studies provided
evidence that the formation of the emulsions may be
associated with LC formation, although the relationship
was clearly complex. The above technique also pointed out
that the presence of the drug may alter the emulsion
characteristics, possibly by interacting with the LC phase].
However, the correlation between the spontaneous
emulsification and LC formation is still not definitely
established.
CHARECTERIASATION OF SMEDDS:
Differential scanning calorimetry
Differential scanning calorimetry for SMEDDS can be
determined using DSC 60. Liquid sample and Solid sample
should be placed in the aluminium pan and result can be
recorded. Any type of chemical interaction should be
determined using DSC.
Fourier transform-infrared spectroscopy
Fourier transform-infrared for SMEDDS can be determined
using FT-IR. Liquid sample should be placed in the liquid
sample holder and result can be recorded. Any type of
chemical interaction should be determined
Using FT-IR..
Macroscopic evaluation
Macroscopic analysis was carried out in order to observe the
homogeneity of microemulsion formulations. Any change in
color and transparency or phase separation occurred during
normal storage condition (37±2ºC) was observed in optimized
microemulsion formulation.
Visual assessment
To assess the self-emulsification properties, formulation (60
mg) was introduced into 100 ml of water in a glass
Erlenmeyer flask at 25°C and the contents were gently stirred
manually. The tendency to spontaneously form a transparent
emulsion was judged as good and it was judged bad when
there was poor or no emulsion formation. Phase diagram was
constructed identifying the good self-emulsifying region.

4. Determination of Self emulsification time
The emulsification time of SMEDDS was determined
according to USP 22, dissolution apparatus 2. 300 mg of each
formulation added drop wise to 500ml purified water at 37ºC.
Gentle agitation was provided by a standard stainless steel
dissolution paddle rotating at 50 rpm. Emulsification time was
assessed visually.
Solubility studies
Unknown amount of selected vehicles was added to each cap
vial containing an excess of drug. After sealing, the mixture
was heated at 40ºC in a water bath to facilitate the
solubilisation. Mixing of the systems was performed using a
vortex mixer. Formed suspensions were then shaken with a
shaker at 25ºC for 48 hours. After reaching equilibrium, each
vial was centrifuged at 3000 rpm for 5 minutes, and excess
insoluble LOV was discarded by filtration using a membrane
filter (0.45 μm, 13 mm, Whatman, India). The concentration
of drug was then quantified by U.V.Spectrophotometer.
Transmittance Test
Stability of optimized microemulsion formulation with respect
to dilution was checked by measuring Transmittance through
U.V. Spectrophotometer (UV-1700 SHIMADZU).
Transmittance of samples was measured at 650nm and for
each sample three replicate assays were performed.
Droplet size determination
It is a precise method for evaluation of stability. Size of
droplet is measured by photon-correlation spectroscopy (PSC)
with Zetasizer. All measurements are carried out at scattering
angle of 90° and 25°C temperatures. Prior to measurement,
microemulsion is diluted in two-steps with pure water then it
is filtered through a 0.22um filter just before it is added to
cuvette. In first step it is diluted with equal amount of water.
In second step the mixture is further diluted to appropriate
concentration for the measurement. That depends on droplet
size (Usually diluted 100-200 times).
Zeta potential measurement
Zeta potential for microemulsion was determined using
Zetasizer HSA 3000 (Malvern Instrument Ltd., UK). Samples
were placed in clear disposable zeta cells and results were
recorded. Before putting the fresh sample, cuvettes were
washed with the methanol and rinsed using the sample to be
measured before each experiment.
Stability
Temperature Stability
Shelf life as a function of time and storage temperature was
evaluated by visual inspection of the SMEDDS system at
different time period. SMEDDS was diluted with purified
distilled water and to check the temperature stability of
samples, they were kept at three different temperature
range (2-8°C (refrigerator), Room temperature) and observed
for any evidences of phase separation, flocculation or
precipitation.
Centrifugation
In order to estimate metastable systems, the optimized
SMEDDS formulation was diluted with purified distilled
water. Then microemulsion was centrifuged (Remi
Laboratories, Mumbai, India) at 1000 rpm for 15 minute at
0°C and observed for any change in homogeneity of
microemulsion.
In vitro release
The quantitative in vitro release test was performed in 900 ml
purified distilled water, which was based on USP 24 method.
SMEDDS was placed in dialysis bag during the release period
to compare the release profile with conventional tablet. 10
ml of sample solution was withdrawn at predetermined time
intervals, filtered through a 0.45 μ membrane filter, dilute
suitably and analysed spectrophotometric ally. Equal amount
of fresh dissolution medium was replaced immediately after
Withdrawal of the test sample. Percent drug dissolved at
different time intervals was calculated using the Bee
Lambert’s equation.
METHOD OF PREPARATION
1. Phase Titration Method: Micro emulsions are prepared by
the spontaneous emulsification method (phase titration
method) and can be depicted with the help of phase diagrams.
Construction of phase diagram is a useful approach to study
the complex series of interaction that can occur when different
components are mixed. Micro emulsions are formed along
with various association structures (including emulsion,
micelles, lamellar, hexagonal, cubic, and various gel and oily
dispersion) depending on the chemical composition and
concentration of each component. The understanding of their
phase equilibrium and demarcation of the phase boundaries
are essential aspects of the study. Because, quaternary phase
diagram (four component system) is time consuming and
difficult to interpret, pseudo ternary phase diagram is
constructed to find the different zones including micro
emulsion zone, in which each corner of the diagram represents
100% of the particular component Fig. 5. The region can be
separated into w/o or o/w micro emulsion by simply
considering the composition that is whether it is oil richor
water rich. Observation should be made carefully so that the
metastable systems are not included. The methodology has
been discussed by Shafiq-un-Nabi etal.
2. Phase inversion Method: Phase inversion of
Micro emulsion occurs upon addition of excess of the
dispersed phase or in response to temperature. During phase
inversion more physical changes occur that include changes in
particle size that can affect drug release in vivo and in vitro.
These methods make use of changing the spontaneous
curvature of the surfactant. For non-ionic surfactant, this can
be achieved by changing the temperature of the system,
forcing a transition from an o/w micro emulsion at low
temperature to a w/o micro
Emulsion at higher temperature. During cooling, the system
crosses a point of zero spontaneous curvature and minimal
surface tension, promoting the formation of finely dispersed
oil droplets. This method is referred to as phase inversion
temperature (PIT) method. Instead of the temperature, other
parameters such as salt concentration or pH value may be
considered instead of the temperature alone. Additionally, a
transition in the spontaneous radius of curvature can be

5. obtained by changing the water volume fraction. By
successively adding water into oil, initially water droplets are
formed in a continuous oil phase. Increasing the water volume
Fraction changes the spontaneous curvature of the surfactant
from initially stabilizing a w/o micro emulsion to o/w micro
emulsion at the inversion locus. Short chain surfactant from
flexible monolayer at the o/w interface resulting in a
bicontinuous micro emulsion at the inversion point.
Fig.1 Pseudo ternary phase diagram of oil, water and
surfactant showing micro emulsion region.
PHASE BEHAVIOUR STUDY
The phase behavior of simple microemulsion system
composing oil, water and surfactant can be studied with the
aid of ternary phase diagram.
Fig.2 Phase Behaviour Study
 WINSOR PHASE :- WI, WII, WIII, WIV
 O :- Oil W:- Water
 L1:- A single phase region of normal micelles or oil
 In water micro emulsion.
 L2:- A reverse micelles or water in oil micro
 Emulsion.
 D: - Anisotropic lamellar liquid crystalline phase.
 μE:- Microemulsion.
The co-surfactant is also amphiphilic with an affinity for
both the oil and aqueous phase. Eg. Alkyl amine, alkanoic
acid, alkaloids, nonionic surfactant, alcohol. A large no.
Of drug molecules are also acts as surface active agent by
themselves, which influence the phase behavior. In this
diagram a corner will represent the binary mixture of two
components such as surfactant/co-surfactant, water/drug
or oil/drug. At low concentration of surfactant there are
certain phases exists in equilibrium. These phases are
referred to as WINSOR PHASES.
 WINSOR-1:- With two phases, the lower (o/w)
microemulsion phase in equilibrium with excess oil.
 WINSOR-2:- With two phases, upper (w/o)
microemulsion phase in equilibrium with excess
water.
 WINSOR-3:- With three phases, middle
microemulsion phase (o/w plus w/o, called bio-
continuous) in equilibrium with upper excess oil and
lower excess water.
 WINSOR-4:- In single phase, with oil, water, and
surfactant homogenously mixed.

6. APPLICATIONS
Enhancement in Solubility and Bioavailability:
Improvement in solubility observed if a drug is loaded in
SMEDDS because it circumvents the solubilisation or
dissolution step in case of class-2 drugs (low solubility/high
permeability). A moderately hydrophobic drug ketoprofen
(Non-steroidal anti-inflammatory drug), is a drug of choice for
sustain release formulation has a side effect of gastric
irritation during chronic therapy. Ketoprofen shows
incomplete release from sustain release formulation due to its
low solubility. Vergote et al. (2001) shows complete release
of ketoprofen from sustains release formulation by loaded it in
nano crystalline form 2, 69 Various formulation approaches
have been used to achieve sustain release, improvement in
bioavailability, and decrease in side effect of gastric irritation
of ketoprofen include preparation of matrix pellets of nano-
crystalline ketoprofen, sustained release ketoprofen
microparticles and formulations, floating oral ketoprofen
systems, and transdermal systems of ketoprofen Different
problems like processing, stability and economic problem
arises during preparation and stabilization of nanocrystalline
or improved solubility forms of drug so by loading drug in
SMEDDS such problems can be overcome. SMEDDS
formulation enhances the bioavailability by increasing
solubility of drug and also decreases the gastric irritation. Also
incorporation of gelling agent in SMEDDS sustains the
release of ketoprofen. In SMEDDS, by the interaction b/w
lipid matrix and water a fine particulate oil-in-water emulsion
will form and this emulsion droplet will deliver the drug in
dissolved form to the gastro intestinal mucosa readily
accessible for absorption. Therefore, increase in AUC i.e.
bioavailability and Cmax is observed with many drugs when
presented in SMEDDS. Supersaturable SMEDDS (S-
SMEDDS): S-SMEDDS have been developed to overcome
the toxic effect of surfactant or GI side effects produced by
surfactant when used in very high concentration as typically
used in SMEDDS. When the formulation is released from an
appropriate dosage form into an aqueous medium, S-
SMEDDS forms a protected supersaturated solution of drug
and this supersaturation is intended to enhance the
thermodynamic activity to the drug inspite its solubility limit,
therefore enhancement in driving force for transit into and
across the biological membrane will be obtain. Reduced level
of surfactant and a polymeric precipitation inhibitor (HPMC
and related cellulose polymers) to yield and stabilize a drug in
a temporarily supersaturated state are contents of S-SMEDDS
formulation. S-SMEDDS of paclitaxel in which HPMC used
as precipitation inhibitor was developed.
Formation of a microemulsion, followed by slow
crystallization of paclitaxel on standing occur in in- vitro
dilution study of S–SMEDDS formulation. This result
indicated that the system was supersaturated with respect to
crystalline paclitaxel, and the supersaturated state was
prolonged by HPMC in the formulation. In the absence of
HPMC, the SMEDDS formulation underwent rapid
precipitation, yielding a low paclitaxel solution concentration.
A pharmacokinetic study showed that the paclitaxel S-
SMEDDS formulation produced approximately a 10-fold
higher maximum concentration (Cmax) and a 5-fold higher
oral bioavailability (F ˜ 9.5%) compared with that of the orally
administered Taxol formulation (F ˜ 2.0%) and the SMEDDS
formulation without HPMC (F ˜ 1%).Reduced quantity of
surfactant can be used with HPMC in order to produce a
temporarily supersaturated state with reduced solubilisation by
applying this approach.
Thus a high free drug concentration would be obtained
through generating and maintaining a supersaturated state in-
vivo and to increase the driving force for absorption. Better
toxicity/safety profile than the conventional SMEDDS
formulation will be obtained by using this approach as S-
SMEDDS contain reduced amount of surfactant. However, the
underlying mechanism of the inhibited crystal growth and
stabilized supersaturation by means of these polymers is
poorly understood even although several studies have been
carried out to investigate this.
Solid SMEDDS: SMEDDS are normally prepared as liquid
dosage forms that can be administrated in soft or hard gelatin
capsules, which have some disadvantages especially in
manufacturing process for soft and leakage problem with hard
gelatin capsules. 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 SEDDS 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, Cmax
and Tmax values. A method of producing self-emulsifying
pellets by wet granulation of a powder mixture composed of
microcrystalline cellulose, lactose and nimesulide as model
drug with a mixture containing mono- and diglycerides,
polisorbate 80 and water has been investigated. The pellets
produced with oil to surfactant ratio of 1:4 (w/w) showed
improved performance in permeation experiments.
Sustain Release from SMEDDS: Due to the wide range of
structures occurring in them, SMEDDS display a rich
behaviour regarding the release of solubilised material. Thus
in case of O/W microemulsion, hydrophobic drugs solubilised
mainly in the oil droplets, experience hindered diffusion and
are therefore released rather slowly (depending on the
oil/water partitioning of the substance). Water soluble drugs,
on the other hand, diffuse essentially without obstruction
(depending on the volume fraction of the dispersed phase) and
are release fast. For balanced microemulsion, relatively fast
diffusion and release occur for both water soluble and oil
soluble drugs due to the bicontinious nature of microemulsion
"structure". Apart from the microemulsion structure, the
microemulsion composition is important for the drug release
rate.

7. Fig. Applications
CONCLUSION -
SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM IS A NOVEL
APPROACH FOR THE FORMULATION OF DRUG COMPOUNDS WITH
POOR AQUEOUS SOLUBILITY. SELF-MICRO EMULSIFYING DRUG
DELIVERY SYSTEMS (SMEDDS) ARE MIXTURES OF OILS,
COSOLVENTS AND SURFACTANTS, WHICH IS ISOTROPIC IN
NATURE. WHEN INTRODUCED INTO AQUEOUS PHASE, IT
EMULSIFIES SPONTANEOUSLY TO PRODUCE FINE O/W EMULSION
UNDER GENTLE AGITATION. SMEDDS REPRESENT A GOOD
ALTERNATIVE FOR THE FORMULATION OF POORLY WATER
SOLUBLE DRUGS. SMEDDS IMPROVE THE DISSOLUTION OF THE
DRUG DUE TO INCREASED SURFACE AREA ON DISPERSION AND
SOLUBILITY EFFECT OF SURFACTANT. THE ORAL DELIVERY OF
HYDROPHOBIC DRUGS CAN BE MADE POSSIBLE BY SMEDDSS,
WHICH HAVE BEEN SHOWN TO SUBSTANTIALLY IMPROVE ORAL
BIOAVAILABILITY. BY THIS APPROACH IT IS POSSIBLE TO
PROLONG THE RELEASE OF DRUG VIA INCORPORATION OF
POLYMER IN COMPOSITION. SMEDDS APPEARS TO BE UNIQUE
&INDUSTRIALLY FEASIBLE APPROACH. WITH FUTURE
DEVELOPMENT.
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