SOLID LIPID NANOPARTICLES

PREPARED BY Dimendra Patel

GUIDED BY Dr. Nazneen Surti

Department of Pharmaceutics Baroda college of pharmacy Limda - vadodara

INTRODUCTION
New approach to deliver lipophilic drug It is same as an oil in water emulsion for parenteral nutrition, but the liquid lipid of the emulsion has been replaced by solid lipid Resulting in the formation of SLN having size range of 100150nm.

 The system consists of spherical solid lipid particles in the nanometer range, dispersed in water or in aqueous surfactant solution. They have ability to carry lipophilic or hydrophilic drugs or diagnostics.

Why Solid Lipid Particle ???

40% of lipophilic drug candidates fail because Their solubility and Formulation stability problem

MERITS: Good biocompatibility Non toxic Stable against Hydrolysis Biodegradable Physically stable Good carrier for lipophillic drugs

Advantages and Disadvantages of various colloidal drug carrier systems

Sr . N o. PROPERTY SLN POLYMER NANOPARTICLES LIPOSOMES LIPID EMULSIONS

1 2 3 4 5 6

Systemic toxicity Cytotoxicity Residues solvents from organic

Low Low No Yes Yes Yes

> or = to SLN > = to SLN Yes No No Yes

Low Low May or may not Yes No < or = to SLN

Low Low No Yes Yes No

Large scale production Sterilization by autoclaving Sustained release

Avoidance of RES

Depend size coating

on and No

Yes

Yes

General ingredients: Solid lipid

Triglycerides (e.g. tristearine, hard fat) Partial glycerides (e.g. Imwitor) Pegylated lipids, Fatty acids (stearic acid) Steroids (e.g. cholesterol) Waxes (e.g. cetylpalmitate) Emulsifier All classes of emulsifiers have been used to stabilize the lipid dispersion. Example :- poloxamer, polysorbates, lecithin and bile acids Water As a aqueous phase

PREPARATION METHODS: High pressure homogenization

Microemulsification- solidification technique

Multiple microemulsion- solidification technique

Ultra sonication or high speed homogenization

PREPARATION METHODS.
SLNs preparation using supercritical fluid SLNs prepared by solvent emulsification/evaporation Spray drying method Double emulsion method

1. HIGH PRESSURE HOMOGENIZATION (HPH)

High pressure homogenizers push a liquid with high pressure (1002000 bar) through a narrow gap (in the range of few microns). The fluid accelerates on a very short distance to very high velocities. The high shear stress disrupts the particles down to the submicron range.
Two type
HOT HOMOGENIZATION TECHNIQUE COLD HOMOGENIZATION TECHNIQUE

HOT HOMOGENIZATION TECHNIQUE

 USE:Lipophilic Insoluble drugs

Not suitable for incorporation of Hydrophilic drugs & Heat Sensitive Drug PROBLEMS:(1) Temperature induced drug degradation

(2) Drug distribution into the aqueous phase during homogenization (3) Complexity of the crystallization step of the nanoemulsion

COLD HOMOGENIZATION TECHNIQUE

 USE:Hydrophilic drugs Thermosensitive Thermolabile drugs.

2. MICROEMULSIFICATION- SOLIDIFICATION TECHNIQUE

Melting of lipid
Preparation of microemulsion by dispersing melted lipid in aqueous medium containing drug under mechanical stirring at 65-70 oC Rapid crystallization of oil droplet on dispersion in cold medium Solid lipid nanoparticles

3. MULTIPLE MICROEMULSION- SOLIDIFICATION

Melting of lipid Add aqueous solution of drug to melted lipid Add Surfactant and co-surfactant at a temperature above the melting point of lipid Formation of clear w/o microemulsion Formed w/o microemulsion is added to a mixture of water, surfactant and co-surfactant under mechanical stirring Formation of suspension of lipid particles Wash with dispersion medium by ultrafiltration system Solid lipid nanoparticles

Other Technique
Ultra sonication or high speed homogenization SLNs preparation using supercritical fluid SLNs prepared by solvent emulsification/evaporation Spray drying method Double emulsion method

CHARACTERIZATION OF SLNs:1. PARTICLE SIZE AND SHAPE 2. PARTICLE CHARGE 3. STRUCTURE

4.

DETERMINATION OF INCORPORATED DRUG

5. IN-VITRO DRUG RELEASE STUDIES 6. RHEOLOGY 7. STORAGE STABILITY

ADVANTAGES :1. High drug levels can be achieved at the site of disease and systemic side effects can be reduced.. 2. Controlling the release profile.. 3. SLN formulation can remain stable for even the years.. 4. Suitable for both hydrophilic and hydrophobic drugs.. 5. Drugs can be protected against chemical degradation by solid matrix of SLN.. 6. Large scale production and sterilization is possible.. 7. SLNs is prepared from physiological lipid which decreases the risk of acute and chronic toxicity..

DISADVANTAGE: Poor drug loading capacity. During storage, drug expulsion after polymeric transition.

Water content of the dispersions is relatively high (7099.9%).

APPLICATION:1. TOPICAL GLUCOCORTICOIDS 2. ANTIANDROGEN

3. SLNs FOR TOPICAL USE

4. ORAL SLNs IN ANTITUBERCULAR CHEMOTHERAPY 5. SLNs AS COSMECEUTICALS 6. SLNs AS GENE VECTOR CARRIER 7. SLNs IN BREAST CANCER AND LYMPH NODE METASTASES 8. SLNs AS A TARGETED CARRIER FOR ANTICANCER DRUG TO SOLID TUMORS

Examples of cosmetic products currently on the market containing lipid nanoparticles.

PRODUCT NAME PRODUCER

Cutanova Cream Nano Repair Q10 Intensive Serum NanoRepair Q10 Cutanova Cream NanoVital Q10

Dr. Rimpler

SURMER Crme Legre Nano-Protection SURMER Crme Riche Nano-Restructurante SURMER Elixir du Beaut Nano-Vitalisant SURMER Masque Crme Nano-Hydratant

Isabelle Lancray

NanoLipid Restore CLR

Chemisches Laboratorium

Nanolipid Q10 CLR Nanolipid Basic CLR NanoLipid Repair CLR

Dr. Kurt Richter, (CLR)

CONCLUSION: Drug molecules into the target site in a controlled manner. Minimizing the problems related to solubility, permeability and toxicity that are associated with the respective drug molecules. High physical stability . Incorporating both the lipophilic and hydrophilic drug molecules makes the SLNs drug delivery system more promising. SLNs Useful for variety of drug molecules including analgesics, antitubercular, anticancer, vitamins, steroids and anti inflammatory agents to the target site.

REFERENCES: Nanoparticulates as drug carriers , Published by Imperial College Press . Solid Lipid Nanoparticles . 217 243

http://en.wikipedia.org/wiki/Solid_lipid_nanoparticle
Westesen K, Bunjes H, Do nanoparticles prepared from lipid solid at room temperature always possess a solid lipid matrix? Int. J. Pharm.115 (1995), 62-69. Mller RH. Mehnert W., Souto EB., 2005. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for dermal delivery. In: Bronaugh, R.L. (Ed.), Percutaneous Absorption, 4th ed, pp. 719738. Eldem T, Speiser P, Hincal A. Optimization of spray-dried and congealed lipid microparticles and characterization of their surface morphology by scanning electron microscopy. Pharm Res 1991; 8:47-54.

THANK YOU.