INTRODUCTION:

Self emulsifying drug delivery system (SEDDS) is defined as isotropic mixture of oil and surfactants or alternatively one or more hydrophilic solvents and co-solvents. Upon mild agitation 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 formulations spread readily in the GI tract and the digestive motility of the stomach and the intestine provide the agitation

necessary for self-emulsification (SEDDS) typically produce emulsion with a droplet size between 100 and 300 nm while SMEDDS form transparent micro emulsion with a droplet size of less than 50 nm. When compared with emulsions which are sensitive and metastable dispersed forms, SEDDS and SMEDDS are physically stable formulations that are easy to manufacture. Microemulsions are currently the subject of many investigations because of their wide range of potential and actual utilizations. The high capacity of microemulsions for drugs makes them attractive formulations for pharmaceuticals. These systems also offer several benefits for oral administration, including increased absorption, improved clinical potency and decreased toxicity. ^[1]Recently, synthesized drug that are being discovered are lipophilic in nature and have poor aqueous solubility, thereby posing problems in their formulation into delivery systems. Because of their low aqueous solubility and low permeability, dissolution and/or release rate from the delivery system forms the rate‐limiting step in their absorption and systemic availability. More than 60% of potential drug products suffer from poor water solubility. For the therapeutic delivery of lipophillic active moieties (BCS class II drugs), lipid based formulations are inviting increasing attention. Currently a number of technologies are available to deal with the poor solubility, dissolution rate and bioavailability of insoluble drugs. In this review article, the various aspects of pharmaceutical SMEDDS where compiled together and target audience are specifically the M.Pharm and B.Pharm students so that their knowledge towards the subject concern can be enhanced and also at the same time can be motivated towards the publication.

IMPORTANCE OF SMEDDS

SMEDDS offer the following importance:-

(i) Irritation caused by prolonged contact between the drug and the wall of the GIT can be surmounted by the formulation of SMEDDS as the microscopic droplets formed help in the wide distribution of the drug along the GIT and these are transported quickly from the stomach.

(ii) Upon dispersion in water, these formulations produce fine droplets with enormous interfacial area due to which the easy partition of the drug from the oil phase into the aqueous phase is possible which cannot be expected in case of oily solutions of lipophilic drugs.

(iii) SMEDDS are advantageous over emulsions in terms of the stability because of the low energy consumption and the manufacturing process does not include critical steps. Simple mixing equipment is enough to formulate SMEDDS and time required for preparation is also less compared to emulsions.

(iv)Poor water soluble drugs which have dissolution rate limited absorption can be absorbed efficiently by the formulation of SMEDDS with consequent stable plasma-time profile. Constant plasma levels of drug might be due to presentation of the poorly soluble drug in dissolved form that bypasses the critical step in drug absorption, that is, dissolution

(v) Along with the lipids, surfactants that are commonly used in the formulation of SMEDDS like Tween 80, Spans, Cremophors (EL and RH40), and Pluronics are reported to have inhibitory action on efflux transporters which help in improving bioavailability of the drugs which are substrates to the efflux pumps. Surfactant named datocopheryl polyethylene glycol 1000 succinate (TPGS) produced by esterification of vitamin E succinate and polyethylene glycol1000 was proved to have inhibitory effect on efflux transporters like P-glycoprotein. The efflux of paclitaxel from the GIT was found to be inhibited with formulation prepared using surfactant named Polysorbate.^[2]

(vi) Drugs which have propensity to be degraded by the chemical and enzymatic means in GIT can be protected by the formulation of SMEDDS as the drug will be presented to the body in oil droplets.

(vii) Microemulsion preconcentrate is advantageous over microemulsion to dispense in the form of liquid filled soft gelatin capsules.

(viii) SMEDDS are advantageous over SEDDS as the former are less dependent on bile salts for the formation of droplets by which better absorption of the drug is expected compared to SEDDS.

(ix) Surfactants of high HLB like Tween 80 are reported to increase the permeability of the drug when administered along with the formulation due to the loosening effect of these on tight junctions.^[3]

ADVANTAGES OF SMEDDS^[4]

Potential advantages of these systems (SMEDDS) include

1. Enhanced oral bioavailability enabling reduction in dose.

2. More consistent temporal profiles of drug absorption.

3. Selective targeting of drug(s) toward specific absorption window in GIT

4. Protection of drug(s) from the hostile environment in gut.

5. Control of delivery profiles.

6. Reduced variability including food effects.

7. Protection of sensitive drug substances.

8. High drug payloads.

9. Liquid or solid dosage forms.

10. Ease of manufacture and scale up.

DISADVANTAGES OF SMEDDS^[5]

1. One of the obstacles for the development of SMEDDS and other lipid-based formulations is the lack of good predicative in vitro models for assessment of the formulations.

2. Traditional dissolution methods do not work, because these formulations potentially are dependent on digestion prior to release of the drug.

3. This in vitro model needs further development and validation before its strength can be evaluated.

4. Further development will be based on in vitro – in vivo correlations and therefore different prototype lipid based formulations needs to be developed and tested in vivo in a suitable animal model.

5. The drawbacks of this system include chemical instabilities of drugs and high surfactant concentrations in formulations (approximately 30-60%) which irritate GIT.

6. Moreover, volatile co solvents in the conventional self-microemulsifying formulations are known to migrate into the shells of soft or hard gelatin capsules, resulting in the precipitation of the lipophilic drugs.

7. The precipitation tendency of the drug on dilution may be higher due to the dilution effect of the hydrophilic solvent.

8. Formulations containing several components become more challenging to validate

TYPES OF MICROEMULSION

Microemulsions are thermodynamically stable, but are only found under carefully defined conditions. According to Winsor, there are four types of microemulsion phases exists in equilibria, these phases are also referred as Winsor phases^[6].

They are,

1. Oil- in- water microemulsion or winsor I

2. Water – in oil microemulsion or winsor II

3. Bi-continuous microemulsion or winsor III

4. Single phase homogeneous mixture or wins or IV

1. Oil- in- water microemulsion or winsor I

In Oil-in-water type of microemulsions droplets of oil is surrounded by a surfactant (and may becosurfactant) film that forms the internal phase distributed in water, which is the continuous phase. This type of microemulsion generally has a larger interaction volume than the w/o microemulsions.

2. Water - in - oil microemulsion or winsor II

In Water-in-oil type of microemulsions droplets of water surrounded by a continuous oil phase. These are recognized as “reverse micelles”, where the polar head groups of the surfactant are facing into the droplets of water, with the fatty acid tails facing into the oil phase. A w/o microemulsion used orally or parenterally may be destabilized by the aqueous biological system.

3. Bi-continuous microemulsion or winsor III

In bicontinuous microemulsion system the amount of water and oil present are similar, In this case, both water and oil exist as a continuous phase. An irregular channel of oil and water are combined, and looks like a “sponge-phase”. Transitions from o/w to w/o microemulsions may pass through this bicontinuous state. Bicontinuous microemulsion, may show non-Newtonian flow and plasticity. These properties make them especially useful for topical delivery of drugs or for intravenous administration

4. Single phase homogeneous mixture or winsor IV

In single phase homogeneous mixture or winsor IV the oil, water and surfactants are homogenously mixed^[7].

COMPOSITIONFOR SMEDDS

1.Drugs

2.Oil phase

3.Surfactant

4.Secondary surfactant (co-surfactant)

5.Co-Solvent

6. Consistency builder

7. Polymers

Various major components of SMEDDS are

1. Drugs

Mainly dugs from BCS II class are used in formulation of the SEDDS includes Ontazolast, Vitamin E, Simvastatin, Tocotrienols Danazol, Itraconazole

2. Oils

Long chain triglyceride and medium chain triglyceride oils with different degree of saturation have been used in the design of SMEDDS. Unmodified edible oils provide the most natural basis for lipid vehicles, but their poor ability to dissolve large amounts of hydrophobic drugs and their relative difficulty in efficient self‐micro emulsification markedly reduces their use in SMEDDS. Recently medium chain triglycerides are replaced by novel semi synthetic medium chain triglycerides containing compound such as Gelucire ,Other suitable oil phases are digestible or non‐digestible oils and fats such as olive oil, corn oil, soya bean oil, palm oil and animal fats etc^[8]

3. Surfactant

Nonionic surfactants with high Hydrophilic Lipophilic Balance (HLB) values are used in formulation of SEDDS. The usual surfactant strength ranges between 30–60% w/w of the formulation in order to form a stable SEDDS. Surfactants have a high HLB and hydrophilicity, which assists 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 relativel high amounts of hydrophobic drug compounds. This can prevent precipitation of the drug within the GI lumen and for prolonged existence of drug molecules

4. Co-surfactant

In SMEDDS, generally co‐surfactant of HLB value 10‐14 is used. Hydrophilic co‐surfactants are preferably alcohols of intermediate chain length such as hexanol, pentanol and octanol which are known to reduce the oil water interface and allow the spontaneous formulation of micro emulsion.

5. Co-solvent

Organic solvents are suitable for oral administration. Examples are ethanol, propylene glycol, and polyethylene glycol, which may help to dissolve large amounts of hydrophilic surfactant or drug in liquid base. Addition of an aqueous solvent such as Triacetin, (an acetylated derivative of glycerol) for example glyceryl triacetate or other suitable solvents act as cosolvents^[9].

6. Consistency builder

Additional material can be added to alter the consistency of the emulsions; such materials include tragacanth, cetyl alcohol, stearic acids and /or beeswax etc

7. Polymers

Inert polymer matrix representing from 5 to 40% of composition relative to the weight, which is not ionizable at physiological pH and being capable of forming matrix are used. Examples are hydroxyl propyl methyl cellulose, ethyl cellulose, etc

RECENT ADVANCEMENTS IN SMEDDS

Recent advancements in the SMEDDS includes^[10].

1. Self‐emulsifying sustained/controlled‐release tablets

2. Self‐emulsifying capsules

3. Self‐emulsifying suppositories

4. Micro emulsion Drug Delivery

5. Self‐emulsifying Nanoparticles

6. Self‐emulsifying sustained/controlled‐release pellets

SOME DRUG DELIVERY SYSTEMS USING SMEDDS

1. Oral delivery:

a) Self emulsifying capsule: After administration of capsules containing conventional liquids SE formulations, microemulsion droplets form and subsequently disperse in the GIT to reach site 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.

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^[11].

c) Self emulsifying sustained / control release pellets: Pellets, as a multiple unit dosage form, possess many advantages over conventional solid dosage form, such as flexiability 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. Serajuddin pointed out that these difficulties could be surmounted by the use of se excipients.

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^[12].

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 industrybecause of the extremely low amount of drug actually delivered as target site.

5. Opthalmic Delivery

In conventional ophthalmic dosage forms, water soluble drugs are delivered in aqueous solution while water insoluble drugs are formulated as suspensions or ointments. Low corneal bioavailability and lack of efficiency in the posterior segment of ocular tissue are some of the serious drawbacks of these systems. Re-cent research efforts have therefore focused on the development of new and more effective delivery systems. Microemulsions have emerged as a promising dosage form for ocular use.

6. Nasal Delivery

Microemulsions are now being studied as a delivery system to enhance uptake across nasal mucosa. Addition of a mucoadhesive polymer helps in prolonging the residence time on the mucosa. Nasal route for ad-ministration of diazepam might be a useful approach for the rapid onset of action during the emergency treatment of status epileptics^[13].

7. Periodontal Delivery

Periodontal disease is a collective term for a number of progressive oral pathological afflictions like inflammation and degeneration of the gums, periodontal ligaments, cementum and its supporting bone. It is a major cause of tooth loss. The invention of Brodin et al. included a novel pharmaceutical composition comprising local anaesthetic in oil form, surfactant, water and optionally a taste masking agent. The composition was in the form of an emulsion or microemulsion and had thermoreversible gelling properties ie it was less viscous at room temperature than after introduction onto a mucous membrane of a patient. The composition could be used as a local anaesthetic for pain relief within the oral cavity in conjunction with periodontal scaling and root planning and overcame the problem with the existing topical products (jelly, ointment or spray) such as lack of efficacy due to inadequate depth of penetration, too short duration and difficulties in administration due to spread, taste etc.

8. Drug Targeting

Drug targeting to diseased cells can be achieved by exploiting the presence of various receptors, anti-gens/proteins on the cell membrane which may be uniquely expressed or over expressed in these cells as compared to the normal cells. Specific antibodies to the surface proteins and ligands for the receptors can be used to target specific cells. Submicron size range of these systems confers excellent opportunities to over-come the physiological barriers and enables efficient cellular uptake followed by intracellular internalization^[14].

DRUG PROPERTIES SUITABLE FOR SMEDDS^[15]

1. Dose should not be so high

2. Drug should be oil soluble

3. High melting point drug is poorly suited to seeds

4. Log P Value should be high.

METHOD OF PREPARATION

The method of making self microemulsion drug delivery system for improve the bioavailability of a drug and pharmaceutical ingredient by emulsifying the drug with the self micro emulsifying excipients various steps as describe below^[16]

1. Phase Titration Method (water titration method)

Microemulsion is prepared by continuous emulsification method and it can be depicted with the help of phase diagram. Forming a phase diagram is a useful approach to study the interaction produced by various structured components are mixed. Microemulsions are formed with the different structures (like emulsion, micelles, lamellar, hexagonal and cubic and various gels and oily dispersion) depending on chemical composition and concentration of each component. The understanding of their phase equilibria and demarcation of the phase boundaries are required aspects of the study. As quaternary phase diagram is time taken and difficult to interpret. Pseudo ternary phase diagram is often constructed to find the different zones having microemulsion zone, in which every corner of diagram shows 100% of the particular component.

2. Phase inversion method

Phase inversion occurred in the microemulsion by adding of excessive amount of dispersion phase or in response to temperature. In this method drastically physical changes occur including change in particle size that can affect the in vivo and in vitro release of drug. These methods make use of changing the spontaneous curvature of the surfactant. For non-ionic surfactants, this can be achieved by changing the temperature of the system, forcing a transition from an o/w microemulsion at low temperature to a w/o microemulsion at higher temperature (transition phase inversion). After cooling, the system crosses a point of zero spontaneous curvature and minimal surface tension, promoting the formulation of finely dispersed oil droplets. This method is called as phase inversion temperature (PIT) method. In place of temperature, other parameter such as salt concentration or pH value may be considered instead of the temperature alone^[17]. Additionally, a transition time 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 change 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.

FACTOR AFFECTING OF SELF-MICROEMULSION

Property of surfactant

Surfactant contains two group lipophilic and hydrophilic groups. Hydrophilic single chain surfactants such as cetylethyl ammonium bromide dissociate completely in dilute solution and have a tendency to form o/w microemulsion. When the surfactant is in presence of salt or when high concentration of surfactant is used, degree of dissociation of polar groups becomes lesser and resulting system may be w/o type^[18].

2. Property of Oil Phase

Oil phase also influence curvature by its ability to penetrate and Swell the tail group region of the surfactant monolayer, swelling of tail results into an increased negative curvature to w/o microemulsion.

3. Packing Ratio

HLB of surfactant determines the type of microemulsion through its influence on packing and film curvature. The analysis of film curvature for surfactant association`s leading to the formation of microemulsion.

4. Temperature

Temperature is extremely important in determining the effective head group size of nonionic surfactants. At low temperature, they are hydrophilic and form normal o/w system. At higher temperature, they are lipophilic and form w/o systems. At an intermediate temperature, microemulsion coexists with excess water and oil phases and forms bicontinuous structure^[19].

CHARACTERIZATION OF SELF MICRO EMULSIONS

The primary means of assessment of SMEDDs is visual observation. The efficiency of self-emulsification could be estimated by determining the rate of emulsification, droplet size distribution and turbidity measurements.

1. Visual assessment:

This may provide important information about the self-emulsifying and micro emulsifying property of the mixture and about the resulting dispersion.

2. Turbidity measurement:

This is to identify efficient self-emulsification by establishing whether the dispersion reaches equilibrium rapidly and in a reproducible time.

3. Determination of emulsification

To promote emulsification in a crude nephelometer, the efficiency of emulsification of various compositions of the Tween 85 and medium-chain triglyceride systems using a rotating paddle has been quantified. This enabled an estimation of the time taken for emulsification was complete, samples were taken for particle sizing by photon correlation spectroscopy, and self-emulsified systems were compared with homogenized systems. The process of self-emulsification was observed using light microscopy. It was concluded that the emulsification process involved erosion of a fine cloud of small particles from the surface of large droplets, rather than a progressive reduction in droplet size.

5. Small-angle neutron scattering

Small-angle neutron scattering can be used to obtain information on the size and shape of the droplets. Small-angle neutron scattering experiments use the interference effect of wavelets scattered from different materials in a sample.

6. Construction of Pseudo ternary phase diagram

The number and types of phases, the % weight of each phase and the composition of the system can be determined by ternary phase diagram. Usually these diagrams are three dimensional but it can be illustrated in two dimensions for ease of drawing and interpretation. On further incorporation of water, these occurs a correlation between emulsification efficiency and region of enhanced water solubilization and phase inversion region, formation of lamellar liquid crystalline dispersion phase. With the help of equilibrium phase diagram, the comparison of different surfactant and their synergy with co-surfactant can be determined. For three component system, phase behavior can be represented by a ternary phase diagram^[21].

EVALUATION OF SMEDDS

The efficiency of self micro emulsification could be estimated by determining the evaluation parameter

1. Droplet Size:

This is a crucial factor in self-emulsification performance because it determines the rate and extent of drug release as well as the stability of the emulsion. Photon correlation spectroscopy, microscopic techniques or a coulter nanosizer are mainly used for the determination of the emulsion droplet size. The reduction of droplet size values below 200 nm lead to the formation of SMEDDS, which are stable, isotropic and clear o/w dispersions

2. Zeta potential measurement

This is used to identify the charge of the droplets. In conventional SEDDS, the charge on an oil droplet is negative due to presence of free fatty acids.

3. Refractive index and percent transmission: Refractive index and percent transmittance proves the clearness of formulation. The refractive index of the SMEDDS is measured by refract meter and compared with that of water. The percent transmittance of the system is measured at particular wavelength using UV-vis spectrophotometer keeping distilled water as blank. If refractive index of system should be similar to that of water. Formulation showing transmittance >99 percent is transparent in nature^[22].

4. Thermodynamic stability studies

a) 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

b) Centrifugation:

Passed formulations are centrifuged thaw cycles between 21 C and +25⁰C with storage at each temperature for not less than 48 h is done at 3500 rpm for 30 min. Those formulations that does not show any phase separation are taken for the freeze thaw stress test.

c) Freeze thaw cycle:

Three freeze for the formulations. Those formulations passed this test showed good stability with no phase separation, creaming, or cracking^[23].

5. Dispersibility test

The efficiency of self-emulsification of oral nano or micro emulsion is assessed using a standard USP XXII dissolution apparatus II. One millilitre of each formulation was added to 500 ml of water at 37 ± 0.5⁰C. A standard stainless steel dissolution paddle rotating at 50 rpm provided gentle agitation. The in vitro performance of the formulations is visually assessed using the following grading system:

Grade A: Rapidly forming (within 1 min) nanoemulsion, having a clear or bluish appearance.

Grade B: Rapidly forming, slightly less clear emulsion, having a bluish white appearance.

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 nano-emulsion when dispersed in GIT. While formulation falling in Grade C could be recommend for SEDDS formulation^[24].

6. Determination of emulsification time. Quantified the efficiency of emulsification of various compositions of the Tween85 and medium-chain triglyceride systems using a rotating paddle to promote emulsification in a crude nephelometer. This enabled an estimation of the time taken for emulsification. Once emulsification was complete, samples were taken for particle sizing by photon correlation spectroscopy, and self-emulsified systems were compared with homogenized systems. The process of self-emulsification was observed using light microscopy. It was clear that the mechanism of emulsification involved erosion of a fine cloud of small particles from the surface of large droplets, rather than a progressive reduction in droplet size^[25].

7. Viscosity Determination

The SMEDDS system is generally administered in soft gelatin or hard gelatin capsules. Therefore, it should be easily pourable into capsules and such system should not be too thick to create a problem. The rheological properties of the micro emulsion are evaluated by Brookfield Viscometer. This viscosity determination confirms whether the system is w/o or o/w. If system has low viscosity then it is o/w type of the system and if high viscosity then it is w/o type of the system

8. Robustness to dilution

Formulations were subjected to 50,100,250 fold dilution with enzyme free simulated gastric fluid pH 1.2; enzyme free simulated intestinal fluid pH 6.8 and distilled water. The resultant diluted emulsions were observed for any physical changes like coalescence of droplets, precipitation or phase separation after 24 hrs^[26].

9. Cloud point measurement

The optimized SMEDDS formulations were diluted with distilled water in the ratio of 1:250. The diluted samples were placed in a water bath and its temperature was increased gradually cloud point was spectrophotmetrically determined as the temperature at which there was a sudden appearance of cloudiness.

10. Drug content determination

Drug from pre-weighed SMEDDS 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^[27].

11. Electron Microscopic Studies:

Freeze-fracture electron microscopy has been used to study the surface characteristics of the SMEDDS. Transmission Electron Microscopy (TEM), Cryo-Transmission Electron Microscopy

APPLICATION OF SMEDDS

1. Super Saturable SMEDDS (SS-SMEDDS)

The high surfactant level typically present in SMEDDS formulation can lead to GI side effects and a new class of supersaturable formulations including supersaturable SMEDDS. (S-SMEDDS) formulations have been de-signed and developed to reduce the surfactant side effects and achieve rapid absorption of poorly soluble drugs^[28].

2. Solid SMEDDS

SMEDDS are normally prepared as liquid dosage forms that can be administrated in soft gelatin capsules, which have some disadvantages especially in the manufacturing process. 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 SMEDDS 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, C max and T max values.

3. Solubilization in SMEDDS

Owing to their frequently high content oil, as well as of surfactant, SMEDDS are usually efficient solubilizers of substances of a wide range of lipophilicity. Thus, the solubilizing capacity of a w/o micro emulsion for water soluble drugs is typically higher than that of an o/w micro emulsion, while the reverse is true for oil soluble drugs. Furthermore, the solubilization depends on the SMEDDS composition^[29].

4. Sustain release from SMEDDS

Due to the wide range of structures occurring in them, SMEDDS display a rich behavior regarding the release of solubilized material. Thus in case of O/W micro emulsion, hydrophobic drugs solubilized 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 micro emulsions, relatively fast diffusion and release occur for both water soluble and oil soluble drugs due to the bicontinuous nature of micro emulsion "structure". Apart from the micro emulsion structure, the micro emulsion composition is important for the drug release rate^[30].

CONCLUSION:

SMEDDS is a system for the enhancement and improvement of the oral bioavailability of lipophilic drugs. As improvement or alternatives of conventional liquid SMEDDS is superior in reducing production cost, simplifying industrial manufacture, and improving patient compliance and stability. SMEDDS is an isotropic mixture of oil, surfactants and cosurfactants, it produce o/w type of emulsion under gentle agitation. SMEDDS protect the labile drug, control drug release and increase drug solubility. In addition, the other side S-SMEDDS is flexible to convert in different solid dosage form for oral and parenteral administration. Moreover, GI irritation is avoidable and controlled/sustained release of drug is achievable. Self‐Micro Emulsifying Drug Delivery Systems appear to be uniqueand industrially feasible approach to overcome the problem of loworal bioavailability associated with the lipophillic drugs. As there is increase in oral drug absorption of BCS II class drugs, so we can sayit is one of the method for enhancing oral bioavailability of drug.

ACKNOWLEDGEMENT:

Authors want to acknowledge the facilities provided by the Rungta College of Pharmaceutical Sciences and Research, Kohka, Kurud Road, Bhilai, Chhattisgarh, India. The authors are also grateful to the e-library of Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India, 490001 for providing UGC-INFLIBNET facility. The authors acknowledge Chhattisgarh Council of Science and Technology (CGCOST) for providing financial assistance under mini research project (MRP) vide letter no. 1124/CCOST/MRP/2015; Dated: September 4, 2015 and 1115/CCOST/MRP/2015; Dated: September 4, 2015.

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Received on 04.03.2017 Modified on 11.04.2017

Research J. Pharm. and Tech. 2017; 10(5): 1563-1570.

DOI: 10.5958/0974-360X.2017.00275.X