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

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.

• 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.

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

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.

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.

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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