Self -emulsifying drug delivery

systems (sedds).

Presented By:-

Mr. Mayur Ravindra Patil.

Sem-1(pharmaceutics)

First Year M. Pharmacy

R.G.SAPKAL COLLEGE OF PHARMACY,

ANJANERI,NASHIK.1

OILS

SURFACTANTCO-

SURFACTANT

DRUG

DEFINITION OF SEDDS:-

Combination Of A

ll

These Makes SEDDS.

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Self-emulsifying drug delivery systems (SEDDS) or self-emulsifying oil formulations (SEOF) are defined as isotropic mixtures of natural or synthetic oils, solid or liquid surfactants, or alternatively, one or more hydrophilic solvents and co-solvents/surfactants.

DEFINITION.

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SEDDS typically produce emulsions with a droplet size between 100 and 300 nm while SMEDDS form transparent micro-emulsions with a droplet size of less than 50 nm. When compared with emulsions, which are sensitive and metastable dispersed forms, SEDDS are physically stable formulations that are easy to manufacture.

INTRODUCTION.

Upon mild agitation followed by dilution in aqueous media, such as GI fluids, these systems can form fine oil−in−water (o/w) emulsions or micro-emulsions(SMEDDS).Self-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.

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NEED FOR SEDDS.

40% of New Drug Candidates show poor aqueous solubility and thus poor bioavailability.

BCS Class II DRUGS (Low solubility-High permeability) – dissolution is rate limiting step for absorption.

E.g. of BCS Class II Drugs:-

Acetylsalicylic Acid, Ibuprofen, Captopril etc.

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SEDDS emulsify spontaneously to produce fine o/w emulsions when introduced into aqueous phase under gentle agitation, provided by the peristaltic motility in GI tract, then absorbed by lymphatic pathways.

HOW SEDDDS ACTS IN BODY??

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1.The nature of the oil/surfactant pair.

2.The surfactant concentration.

3.Oil/surfactant ratio.

4.The concentration and nature of co-surfactant and surfactant/co-surfactant ratio.

5.Temperature at which self micro-emulsification occurs.

FORMULATION CONSIDERATIONS.

The Self-Emulsification Process Is Specific To The-

EXCEPIENTS USED IN SEDDS.1.Oils:-

The oil represents one of the most important excipients in the SEDDS formulation not only because it can solubilise marked amounts of the liphophilic drug or facilitate self-emulsification but also and mainly because it can increase the fraction of liphophilic drug transported via the intestinal lymphatic system, thereby increasing absorption from the GI tract depending on the molecular nature of the triglyceride.

E.g.1. Triglyceride .

2.Hydrolyzed corn oil

3.dl-alpha tocopherol

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4.Fractionated triglyceride of palm seed oil (medium-chain triglyceride)

5.Mixture of mono-and di-glycerides of caprylic/capric acid Medium chain mono-and di-glycerides

6.Corn oil

7.Olive oil

8.Oleic acid

9.Sesame oil

10.Hydrogenated soybean oil

The most widely recommended ones being the non-ionic surfactants with a relatively high hydrophilic−liphophilic balance (HLB). The commonly used emulsifiers are various solid or liquid ethoxylated polyglycolyzed glycerides and polyoxyethylene 20 oleate (Tween 80).

Usually the surfactant concentration ranges between 30 and 60% w/w in order to form stable SEDDS.

2.surfactants.

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E.g. 1. Polyglycolyzed glycerides (HLB = 1−14)

2. Polyglycolyzed glycerides, POE−castor oil derivative

3. Maisine 35−1, Cremophor EL

The surfactant involved in the formulation of SEDDS should have a relatively high HLB and hydrophilicity so that immediate formation of o/w droplets and/or rapid spreading of the formulation in the aqueous media (good self-emulsifying performance) can be achieved. For an effective absorption, the precipitation of the drug compound within the GI lumen should be prevented and the drug should be kept solubilised for a prolonged period of time at the site of absorption.

4.Polysorbate 20 (Tween 20)

5.Polysorbate 80 (Tween 80)

6.D‐alpha Tocopheryl polyethylene glycol 1000 succinate (TPGS)

7.Polyoxy‐35‐castor oil(Cremophore RH40)

8.Polyoxy‐40‐ hydrogenated castor oil(Cremophore RH40)

9.Labrasol

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2.co-surfactants.

The production of an optimum SEDDS requires relatively high concentrations (generally more than 30% w/w) of surfactants. 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. On the other hand, alcohols and other volatile co-solvents have the disadvantage of evaporating into the shells of the soft gelatine, or hard, sealed gelatine capsules in conventional SEDDS leading to drug precipitation.

E.g.:- 1.Span 20.

2.Span 80.

3.Capryol 90.

4.Lauroglycol.

5.Transcutol.

7.Capmul.

6.Ethanol.

8.Polypylene glycol.

9.Polyethylene glycol.

self-emulsification takes place when the entropy change favouring dispersion is greater than the energy required to increase the surface area of the dispersion.

The free energy of a conventional emulsion formulation is a direct function of the energy required to create a new surface between the oil and water phases.

The two phases of the emulsion tend to separate with time to reduce the interfacial area and thus the free energy of the systems.

MECHANISM OF SELF-EMULSIFICATION.

Free energy in the micro-emulsion formation is directly proportional to the energy required to create new surface between the two phases, and is given by the equation-

Where, ΔG=Free energy associated with the process.

N=No. of droplets of radius r.

σ=Represents interfacial energy.

ΔG=Σ Nπr²σ

DIFFERENCE BETWEEN SEDDS AND SMEDDS.

1. HIGHER SURFACTANT AND CO-SURFACTANT /OIL RATIO:-

SEDDS SMEDDS

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2.GLOBULE SIZE.

SEDDS SMEDDS

100-300 nm <50 nm

40-80% <20%

3.Concentration of oil.

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TYPES OF S-SEDDS.

CAPSULES

TABLETS

PELLETS

POWDERS IMPLANTS

SOLID DISPERSIONS

SOLID SELF-EMULSIFYING DOSAGE FORMS.

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SOLID

SEDD

S

Combines advantages of lipid based drug delivery systems with that of solid dosage form.

Overcomes shortcomings of liquid formulations.

Eg.SE Tablets of Diclofenac, Indomethacin etc.

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advantages of s-seeds.

DRUG. TRADE NAME/COMPANY.

TYPE OF FORMULATION.

INDICATION.

Cyclosporin A Neoral,Sandimmune (Novartis)

Soft gelatin capsule

Immuno-suppressant

Ritonavir Norvir(Abbott) Soft gelatin capsule

HIV Antiviral

Sanquinavir Fortovase(Roche)

Soft gelatin capsule

HIV Antiviral

Valproic acid Convulex (Pharmacia)

Soft gelatin capsule

Anti-epileptic

MARKETED ORAL SOLID SEDDS.

EVALUATION parameters of seeds.

1.Thermodynamic stability studies.

A. Heating cooling cycle.

B. Centrifugation.

C. Freeze thaw cycle.

2.Dispersibility test.

3.Turbidimetric Evaluation.

4.Viscosity Determination.

5.Droplet Size Analysis Particle Size Measurements.

6.Refractive Index and Percent Transmittance.

7.Electro conductivity Study.

8.In Vitro Diffusion Study.

9.Drug content.

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Improvement in Solubility and bioavailability.

APPLICATIONS.

Protection against Biodegradation.

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Self-emulsifying drug delivery systems are a promising approach for the formulation of drug compounds with poor aqueous solubility.

The oral delivery of hydrophobic drugs can be made possible by SEDDSs, which have been shown to substantially improve oral bioavailability.

With future development of this technology, SEDDSs will continue to enable novel applications in drug delivery and solve problems associated with the delivery of poorly soluble drugs.

CONCLUSION.

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References.

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1.R Neslihan Gursoy, Simon Benita,.”Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of liphophilic drugs”;Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Ankara, Turkey; The Hebrew University of Jerusalem, School of Pharmacy, Department of Pharmaceutics, 91120 Jerusalem, Israel Received 10 February 2004

2.Patel Nitesh N.,Rathva Sunil., Mr.ShahViral;Dr. Upadhyay Umesh, ”Review on Self Emulsifying Drug Delivery System Novel Approach for Solubility Enhancement”Sigma institute Of Pharmacy1, Department Of Pharmaceutics, Vadodara, Gujarat, INDIA

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3.Kommuru TR, Gurley B, Khan MA, Reddy IK. Self‐emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int J Pharm 2001;212: 233‐46.

5.http://www.sciencedirect.com/science/article/pii/S0753332204000319

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