SOLID LIPID NANOPARTICLES

PREPARED BY:- SHREESHAIL TUMBAGI

1ST M.PHARMACY

PHARMACETICS

ABMRCP-107

CONTENTS: -

INTRODUCTION

DEFINITION

METHOD OF PREPARATIONS

EVALUATION

ADVANTAGES

DISADVANTAGES

APPLICATION

REFERENCES2

INTRODUCTION :-

Solid lipid nanoparticles (SLN) are a new pharmaceutical delivery

system or pharmaceutical formulation

Solid lipid nanoparticles possess a solid lipid core matrix that can

solubilize lipophilic molecules. The lipid core is stabilized

by surfactants (emulsifiers)

Solid lipid nanoparticles are spherical in shape & diameter range from 10-1000nm.

They are manufactured from synthetic/natural polymers and ideally suited to

optimize drug delivery and reduce toxicity3

Structure of solid lipid nanoparticle (SLN)

DEFINITION :-

• The Solid Lipid Nanoparticles (SLN’S) Are Submicron Colloidal Carriers Which

Are Composed Of Physiological Lipid, Dispersed In Water Or In An Aqueous

Surfactant Solution

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METHOD OF PREPARATIONS :-SLNs are made up of solid lipid, emulsifier and water/solvent. The lipids used may be triglycerides (tri-

stearin), partial glycerides, fatty acids (stearic acid, palmitic acid), and steroids (cholesterol) and waxes

(cetyl palmitate).

Different methods of SLNs preparation :-

o High shear homogenization:

Hot homogenization

Cold homogenization

o Ultra sonication / high speed homogenization:

Probe ultra sonication

Bath ultra sonication

o Solvent emulsification/evaporation

o Micro emulsion based SLN preparations

o SLN preparation by using supercritical fluid

o Spray drying method

o Double emulsion method

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HIGH SHEAR HOMOGENIZATION:-

It is A reliable and powerful technique, which is used for the production of slns.

High pressure homogenizers push A liquid with high pressure (100–2000 bar)

through A narrow gap (in the range of A few microns). The fluid accelerates on A

very short distance to very high velocity (over 1000 km/H). Very high shear stress

and cavitation forces disrupt the particles down to the submicron range. Generally

5 -10% lipid content is used but up to 40% lipid content has also been investigated.

Two general approaches of HPH are :-

Hot Homogenization.

Cold Homogenization.

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HOT HOMOGENIZATION :- COLD HOMOGENIZATION :-

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ULTRA SONICATION OR HIGH SPEED HOMOGENIZATION :-

SLN were also developed by high speed stirring or sonication.

The problem of this method is broader particle size distribution ranging into

micrometre range.

This lead physical instabilities likes particle growth upon storage. Potential

metal contamination due to ultra sonication is also a big problem in this

method.

So for making a stable formulation, studies have been performed by various

research groups that high speed stirring and ultra sonication are used combined

and performed at high temperature.9

SPRAY DRYING METHOD :-

It’s an alternative procedure to lyophilisation in order to transform an aqueous

SLN dispersion into a drug product.

It’s a cheaper method than lyophilisation.

This method cause particle aggregation due to high temperature, shear forces

and partial melting of the particle

SLN PREPARED BY SOLVENT EMULSIFICATION/EVAPORATION :-

For the production of nanoparticle dispersions by precipitation in o/w

emulsions. The lipophilic material is dissolved in water-immiscible organic

solvent (cyclohexane) that is emulsified in an aqueous phase.

Upon evaporation of the solvent nanoparticle dispersion is formed by

precipitation of the lipid in the aqueous medium.

The mean diameter of the obtained particles was 25 nm with cholesterol acetate

as model drug and lecithin/sodium glycocholate blend as emulsifier10

INGREDIENTS USED IN THE PREPARATION OF SLN :-

Name of the ingredients concentration

Lipid 3.33% w/v

Phospholipids 0.6-1.5%

Glycerol 2-4%

Poloxamer 188 1.2-5% w/w

Soy phosphatidyl choline 95%

Compritol 10%

Cetyl palmitate 10% w/w

Tego care 450 (surfactant) 1.2% w/w

PEG 2000 0.25%

PEG 4500 0.5%

Tween 85 0.5%

Ethyl oleate 30%

Na alginate 70%

Ethanol/butanol 2%11

EVALUATION :-

EX VIVO METHODS :-

A large number of drugs including very hydrophilic molecules have been

postulated to be

incorporated into SLN.

Various methods used to study the in vitro release of the drug are:

• side by side diffusion cells with artificial or biological membrane.

• Dialysis bag diffusion technique.

• reverse dialysis bag technique.

• Agitation followed by ultracentrifugation or centrifugal ultra filtration.12

IN VITRO DRUG RELEASE :-

DIALYSIS TUBING:-

In vitro drug release could be achieved using dialysis tubing. The solid lipid nanoparticle

dispersion is placed in pre - washed dialysis tubing which can be hermetically sealed. The

dialysis sac then dialyzed against a suitable dissolution medium at room temperature; the

samples are withdrawn from the dissolution medium at suitable intervals, centrifuged and

analyzed for the drug content using a suitable analytical method.

REVERSE DIALYSIS:-

In this technique a number of small dialysis sacs containing 1 ml of dissolution medium are

placed in SLN dispersion. The SLN’s are then displaced into the medium.13

ADVANTAGES

Control And/or Target Drug Release.

Improve Stability Of Pharmaceuticals.

High And Enhanced Drug Content (Compared To Other Carriers).

Feasibilities Of Carrying Both Lipophilic And Hydrophilic Drugs.

Most Lipids Being Biodegradable, SLN’s Have Excellent Biocompatibility.

Water Based Technology (Avoid Organic Solvents).

Easy To Scale-up And Sterilize.

More Affordable (Less Expensive Than Polymeric/Surfactant Based Carriers).

Easier To Validate And Gain Regulatory Approval.

Much Easier To Manufacture Than Bio Polymeric Nanoparticles.

No Special Solvent Required.

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DISADVANTAGES

› Particle growth.

› Unpredictable gelation tendency.

› Unexpected dynamics of polymeric transitions.

› Sometimes burst release.

APPLICATION

Used as Target drug delivery system.

Used in Topical use, cosmeceuticals.

Targeted carrier for anticancer drug to solid tumours.15

REFERENCES :-

• SAUPE, ANNE; RADES, THOMAS (2006). "NANOCARRIER TECHNOLOGIES".

P. 41. DOI:10.1007/978-1-4020-5041-1_3.

• JENNING, V; THUNEMANN, AF; GOHLA, SH (2000). "CHARACTERISATION OF A

NOVEL SOLID LIPID NANOPARTICLE CARRIER SYSTEM BASED ON BINARY

MIXTURES OF LIQUID AND SOLID LIPIDS". INTERNATIONAL JOURNAL OF

PHARMACEUTICS 199 (2): 167–77

• S. MUKHERJEE*, S. RAY AND R. S. THAKUR, SOLID LIPID NANOPARTICLES: A

MODERN FORMULATION APPROACH IN DRUG DELIVERY SYSTEM.

• HTTP://EN.WIKIPEDIA.ORG/WIKI/SOLID_LIPID_NANOPARTICLE16

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