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SOLID LIPID NANOPARTICLE AS PROMISING DRUG DELIVARY SYSTEM

DEPARTMENT OF PHARMACEUTICS

ANURADHA COLLEGE OF PHARMACY, CHIKHLI.

2011-2012.

Seminar on: Recent Trends in Pharmaceutical Sciences

Presented by:Gajanan S.Ingole

Guided by:Mr. K.B.Charhate

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Introduction

Advantages & disadvantages

Aims of SLNs

Principal of drug release

Methods of Preparation

Analytical characterization of SLNs

Applications of SLNs

Routes of administration

References

CONTENTS :

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Solid lipid nanoparticles

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.

They consist of macromolecular materials in which the active principle is dissolved, entrapped, and or to which the active principle is adsorbed or attached.

No potential toxicity problems as organic solvents are not used.

SLNs are spherical in shape & diameter range from 10-1000nm.

To overcome the disadvantages associated with the liquid state of the oil droplets, the liquid lipid was replaced by a solid lipid shown in fig,

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The reasons for the increasing interest in lipid based system are :

1. Lipids enhance oral bioavailability and reduce plasma profile variability.

2. Better characterization of lipoid excipients.

3. An improved ability to address the key issues of technology transfer and

manufacture scale-up.

Fig. 1: Structure of solid lipid nanoparticle (SLN)

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Advantages of SLN

1) Control and target drug release.

2) Excellent biocompatibility.

3) Improve stability of pharmaceuticals.

4) High and enhanced drug content.

5) Easy to scale up and sterilize.

6) Enhanced bioavailability of entrapped bioactive compounds.

7) Much easier to manufacture than biopolymeric nanoparticles.

8) No special solvent required.

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9) Conventional emulsion manufacturing methods applicable.

10) Raw materials essential the same as in emulsions.

11) Can be subjected to commercial sterilization procedures.

Disadvantages of SLN

1) Particle growth.

2) Unpredictable gelation tendency.3) Unexpected dynamics of polymeric transitions

Aims of solid lipid nanoparticles

3) Possibility of controlled drug release.

4) Increased drug stability.

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3) High drug pay load.

4) No bio-toxicity of the carrier.

5) Avoidance of organic solvents.

6) Incorporation of lipophilic and hydrophilic drugs.

Principles of drug release from SLNs

The general principles of drug release from lipid nanoparticles are as 1. Crystallinization behaviour of the lipid carrier and high mobility of

the drug lead to fast drug release.

2. Higher surface area due to smaller particle size in nanometer range gives higher drug release.

3. Slow drug release can be achieved when the drug is homogenously dispersed in the lipid matrix. It depends on type and drug entrapment model of SLN.

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Methods of preparation of solid lipid nanoparticles

1. High pressure homogenization

A. Hot homogenization

B. Cold homogenization

2. Ultrasonication

A. Probe ultrasonication

B. Bath ultrasonication

3. Solvent evaporation method

4. Solvent emulsification-diffusion method

5. Microemulsion based method

6. Spray drying method

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7. Double emulsion method

8. Precipitation technique

9. Film-ultrasound dispersion

First method to prepare solid lipid nanoparticle are as

1. High pressure homogenization

A. Hot homogenization

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Fig: Solid lipid nanoparticles preparation by hot homogenization process

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B. cold homogenization process

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2. Ultrasonication/high speed homogenization

SLNs are also prepared by ultrasonication or high speed homogenization

techniques.

For smaller particle size combination of both ultrasonication and high

speed homogenization is required

Advantages

Reduced shear stress.

Disadvantages

Potential metal contamination.

Physical instability like particle growth upon storage.

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3. Solvent evaporation

4. Solvent emulsification-diffusion method

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5. Microemulsion based method

Fig. : Microemulsion method

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6. Spray drying method

It's an alternative procedure to lyophilization in order to transform

an aqueous NLC dispersion into a drug product.

It's a cheaper method than lyophilization. But his method can

cause particle aggregation due to high temperature, shear forces and

partial melting of the particle.

7. Double emulsion method

Here the drug is encapsulated with a stabilizer to prevent the

partitioning of drug in to external water phase during solvent evaporation

in the external water phase of w/o/w double emulsion.

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8. Precipitation method

The glycerides are dissolved in an organic solvent (e.g.

chloroform) and the solution will be emulsified in an aqueous phase.

After evaporation of the organic solvent the lipid will be precipitated

forming nanoparticles.

9. Film-ultrasound dispersion

lipid + drug add in to organic solutions, after decompression,

rotation and evaporation of the organic solutions, a lipid film is formed.

Then the aqueous solution which includes the emulsions was added,

Using the ultrasound with the probe to diffuser at last, the SLN with the

little and uniform particle size is formed.

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1) Measurement of particle size

Static light scattering (SLS)

Electron microscopy

Acoustic methods.

Atomic force microscopy (AFM)

DSC

Analytical characterization of SLN

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2) Measurement of crystallinity & lipid modification

X-ray photoelectron spectroscopy

Laser doppler anaemometry

DSC

Gel chromatography

Electrophoresis.

DSC.

IR.

X-ray scattering.

Raman spectroscopy

3) Co – existence of additional structures

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Routes of administration

1. Parenteral administration

2. Oral administration

3. Rectal administration

4. Nasal administration

5. Respiratory delivery

6. Ocular administration

7. Topical administration

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1. SLN as potential new adjuvant for vaccines.

2. Solid lipid nanoparticles in cancer chemotherapy.

3. Solid lipid nanoparticles for delivering peptides and proteins.

4. Solid lipid nanoparticles for targeted brain drug delivery.

5. Solid lipid nanoparticles for parasitic diseases.

6. Solid lipid nanoparticles for ultrasonic drug and gene delivery.

7. SLN applied to the treatment of malaria.

8. Solid lipid nanoparticles in tuberculosis disease.

9. SLN in cosmetic and dermatological preparations.

10. SLN for potential agriculture applications

Applications of SLN

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Vyas S.P. and Khar R.K. Targeted And Controlled Drug Delivery System, 1stEdition, 2002, CBS Publication; 249 - 277.

Jain N. K., Controlled and novel Drug Delivery, 1st edition 2001, CBS Publication; 292 - 301.

Mukherjee S., Ray S., Thakur R.S. “ Solid lipid nanoparticles: a modern formulation approach in drug delivery system” Indian journal of Pharmaceutical sciences, 71(2009) 349-358.

Heurtault B., Saulnier P., Pech B., Proust J.E., Benoit J.P. “ Physico-chemical stability of colloidal lipid particles’’ Biomaterials 24 (2003) 4283-4300

REFERENCE

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Feng S., Chien S. “ Chemotherapeutic engineering: application and further development of chemical engineering principles for chemotherapy of cancer and other diseases” Chemical engineering science 58 (2003) 4087-4114.

Gasco M.R. “ Lipid nanoparticles: perspectives and challenges”Advanced drug delivery reviews, 59 (2007)

377-378. Muller R.H., Mader K., Gohla S. “ Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of art” European journal of Pharmaceutics & Biopharmaceutics, 50 (2000) 161-177

Kaur I.P., Bhandari R., Bhandari S., Kakkar V. “ Potential of Solid lipid nanoparticles in brain targeting” Journal of Controlled release, 127 (2008) 97-109