NIOSOMESSupervised by :Dr. Roshan IsaraniH.O.D of Pharmaceutics

Submitted by:Sunil SainiM.pharm(P`ceutics) Sem-2nd

LACHOO MEMORIAL COLLEGE OF SCIENCE AND TECHNOLOGY

JODHPUR

PRESENTATION FLOW

Introduction

Methods of Preparation

Evaluation of Niosomes

Applications of Niosomes

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1. Introduction

NIOSOMES Niosomes are a novel drug delivery system, in which the

medication is encapsulated in a vesicle composed of a bilayer of non-ionic surface active agents .

These are very small, and microscopic in size that lies in the nanometric scale. Although structurally similar to liposomes, they offer several advantages over them.

Niosomes have recently been shown to greatly increase transdermal drug delivery and also in targeted drug delivery.

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WHY ? WHY? WHY?

Used for a variety of drugs : includes hydrophilic, lipophilic as well as amphiphilic moieties.

Act as a depot to release the drug slowly and offer a controlled release.

Osmotically active and stable. Increase the stability of the entrapped drug. Handling and storage of surfactants do not require any special

conditions Enhance the skin penetration of drugs.

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Structure of Niosomes

Niosomes are microscopic lamellar structures, which are formed on the admixture of non-ionic surfactant of the alkyl or dialkyl polyglycerol ether class and cholesterol with subsequent hydration in aqueous media.

Niosomes may be unilamellar or multilamellar depending on the method used to prepare them.

The hydrophilic ends are exposed on the outside and inside of the vesicle, while the hydrophobic chains face each other within the bilayer.

Hence, the vesicle holds hydrophilic drugs within the space enclosed in the vesicle, while hydrophobic drugs are embedded within the bilayer itself.

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Contd…

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SmallUnilamellarVesicle (SUV)

LargeUnilamellarVesicle (LUV)

MultilamellarVesicle (MLV)

Typical Size Ranges: SLV: 20-50 nm – MLV:100-1000 nm7

Niosomes Vs Liposomes

In both basic unit of assembly is Amphiphiles, but they phospholipids in liposomes and nonionic surfactants in niosomes.

Both can entrap hydrophilic and lipophilic drugs. Both have same physical properties but differ in their chemical

composition. Niosomes has higher chemical stability than liposomes. Niosomes made of uncharged single chain surfactant molecules Liposomes made of neutral or charged double chain

phospholipids.

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Advantages : Niosomes Over Liposomes

• Ester bonds of phospholipids are easily hydrolyzed, this can lead to phosphoryl migration at low PH.

• Peroxidation of unsaturated phospholipids. • As liposomes have purified phospholipids they are to be stored

and handled at inert(N2) atmospheres where as Niosomes are made of non ionic surfactants and are easy to handle and store.

• Phospholipid raw materials are naturally occurring substances and as such require extensive purification thus making them costly.

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Niosomes : Types

1.Bola-Surfactant containing Niosomes:

Niosomes made of alpha,omega-hexadecyl-bis-(1-aza-18-crown-6) (Bola-surfactant)-Span 80-cholesterol (2:3:1 molar ratio) are named as Bola-Surfactant containing Niosomes.

2. Proniosomes:

A dry product which may be hydrated immediately before use to yield aqueous Niosome dispersions. These ‘proniosomes’ minimize problems of Niosome physical stability such as aggregation, fusion and leaking, and provide additional convenience in transportation, distribution, storage, and dosing.

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Formation of niosomes from proniosomes

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Factors Affecting Niosomes Formation

Factors affecting niosomes formation

Non-ionic surfactant

nature

Membrane additives

Nature of encapsulated

drug

Surfactants and lipid

levels

Hydration Temperature

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Contd…

Nature of non-ionic surfactant

Type of surfactant influences encapsulation efficiency, toxicity, and stability of niosomes.

SURFACTANT

Hydrophobic tail Hydrophilic headLinked via ether , amide or ester bonds

Consist of one or two alkyl or perfluroroalkyl groups or in some

cases a single steriodal group.

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Contd…

• The alkyl group chain length is usually from C12-C18

• Span surfactants with HLB values between 4 and 8 were found to be compatible with vesicle formation

• The water soluble detergent polysorbate 20 (HLB value 16.7) also forms niosomes with cholesterol

• Polyglycerol monoalkyl ethers and polyoxylate analogues are the most widely used single-chain surfactants.

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Contd…

Membrane additives• Cholesterol, a natural steriod, is the most commonly used

membrane additive• Usually incorporated in 1:1 molar ratio• Prevent vesicle aggregation by the inclusion of molecules that

stabilize the system against the formation of aggregates by repulsive steric or electrostatic effects

• Leads to the transition from the gel state to liquid phase in niosomes systems

• As the result, niosomes become less leakyCholesterol

Dicetyl phosphate provides negative charge to vesicles. It is used to prevent aggregation of hexadecyl diglycerol ether (C16G2) niosomes.Stearic acid is used in the preparation of cationic niosomes

• Dicetyl phosphate• Stearic acid

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Contd…

Surfactant and lipid levels• The surfactant/lipid ratio is generally 1:1• If the level of surfactant/lipid is too high, increasing the

surfactant/lipid level increases the total amount of drug encapsulated.

Hydration temperature• The hydrating temperatures used to make niosomes should

usually be above the gel to liquid phase transition temperature of the system

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2. Methods Of Preparation

• Ether injection method

• Film method

• Sonication

• Reverse phase evaporation

• The “Bubble” method

• Micro fluidization.

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Contd…

Ether injection method• Slow injection of an ether solution of niosomal ingredients

into an aqueous medium at high temperature• A mixture of surfactant and cholesterol (150 μmol) is

dissolved in ether (20 ml) and injected into an aqueous phase (4 ml) using a 14- gauge needle syringe

• Temperature of the system is maintained at 60oC during the process

• Niosomes in the form of large unilamellar vesicles (LUV) are formed.

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Contd…

Film method• The mixture of surfactant and cholesterol is dissolved in an

organic solvent (e.g. diethyl ether, chloroform, etc.) in a round-bottomed flask

• The organic solvent is removed by low pressure/vacuum at room temperature

• The resultant dry surfactant film is hydrated by agitation at 50-60oC

• Multilamellar vesicles (MLV) are formed.

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Contd…

Sonication• The aqueous phase is added into the mixture of surfactant and

cholesterol in a scintillation vial• Homogenized using a sonic probe• The resultant vesicles are of small unilamellar (SUV) type

niosomes• The SUV type niosomes are larger than SUV liposomes• It is possible to obtain SUV niosomes by sonication of MLV

type vesicles.

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Contd…

Reverse phase evaporation• Surface-active agents are dissolved in chlorofom, and 0.25

volume of phosphate saline buffer (PBS) is emulsified to get w/o emulsion

• The mixture is sonicated and subsequently chloroform is evaporated under reduced pressure

• The surfactant first forms a gel and then hydrates to form niosomal vesicles

• The vesicles formed are unilamellar and 0.5 μ in diameter.

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Contd…

The “Bubble” method It is novel technique for the one step preparation of liposomes

and niosomes without the use of organic solvents The bubbling unit consists of round-bottomed flask with three

necks positioned in water bath to control the temperature Water-cooled reflux and thermometer are positioned in the

first and second neck and nitrogen supply through the third neck

Cholesterol and surfactant are dispersed together in the buffer (pH 7.4) at 70°C, the dispersion mixed for 15 secs with high shear homogenizer and immediately afterwards “bubbled” at 70°C using nitrogen gas.

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Contd…

Micro fluidization This is a recent technique to prepare small MLVS A microfludizer is used to pump the fluid at a very high

pressure (10,000 psi) through a 5 pm screen It is then forced along defined micro channels, which direct

two streams of fluid to collide together at right angles, thereby affecting a very efficient transfer of energy

The lipids/surfactants can be introduced into the fluidizer The fluid collected can be recycled until spherical vesicles are

obtained Uniform and small sized vesicles are obtained

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3. Evaluation of Niosomes

• Optical microscopy

• Particle size determination

• Removal of unentrapped drug

• Percentage drug entrapment

• Drug content analysis

• Invitro release study

• Stability studies

• Partition coefficient24

Evaluation of niosoms

Entrapment efficiency Depend on the method of preparation Niosomes prepared by ether injection method have better

entrapment efficiency than those prepared by the film or sonication

Addition of cholesterol to non-ionic surfactants with single- or dialkyl-chain significantly alters the entrapment efficiency

Surfactants of glycerol type lead to reduction in entrapment capacity as the amount of cholesterol increases

Niosomes in the form of liquid crystals possess better entrapment efficiency than gel type vesicles

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contd…

Entrapment efficiency (EF)=(Amount entrapped/total amount) x100 Niosomes, similar to liposomes, assume spherical shape and so their

diameter can be determined using light microscopy, photon correlation microscopy and freeze fracture electron microscopy.

Freeze thawing (keeping vesicles suspension at –20°C for 24 hrs and then heating to ambient temperature) of niosomes increases the vesicle diameter, which might be attributed to fusion of vesicles during the cycle.

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contd…

In-vitro release A method of in-vitro release rate study includes the use of dialysis

tubing. A dialysis sac is washed and soaked in distilled water. The vesicle

suspension is pipetted into a bag made up of the tubing and sealed. The bag containing the vesicles is placed in 200 ml of buffer solution in a 250 ml beaker with constant shaking at 25°C or 37°C.

At various time intervals, the buffer is analyzed for the drug content by an appropriate assay method of vesicles during the cycle.

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4. Applications Of Niosomes

Applications

Transdermal Parenteral Peroral Radiopharm-aceuticals

Opthhalmic Drug

delivery

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THANK YOU

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