SOLID LIPID NANOPARTICLES

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nanoparticulate drug delivery system.

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SOLID LIPID NANOPARTICLES :

SOLID LIPID NANOPARTICLES Delivered by – Amol Amrutkar Department – Industrial pharmacy Guided by- mr.v.k.chatap

CONTENT:

CONTENT Introduction of Nanoparticles Solid lipid Nanoparticles Advantage & disadvantages of SLNs Methods of Preparation Sterilization Criteria Characterization of SLNs Applications of SLNs References

INTRODUCTION:

INTRODUCTION NANOTECHNOLOGY- It comprises technological developments on the nanometer scale, usually 0.1 to 100 nm. Nanotechnology , the science of the small. Nano is Greek for dwarf, and nanoscience deals with the study of molecular and atomic particles.

The application of nanotechnology in pharmaceutical field.:

The application of nanotechnology in pharmaceutical field. NANOSUSPENSIONS : They are colloidal dispersions of nanosized drug particle that are produced by suitable method and stabilized by suitable stabilizer . NANOPARTICLES : They are solid colloidal particles sized from 30-100 nm . NANOSPHERES : Polymer matrices in which drug is dissolved or dispersed . NANOCAPSULES : C onsists of polymer wall entrapping an oily core in which the drug is dissolved

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NANOPARTICLES : Nanoparticles are particles made of natural or synthetic polymers ranging in size from 50 to 500 nm. They consist of macromolecular materials in which the active principle ( drug or biologically active material ) is dissolved, entrapped, and or to which the active principle is adsorbed or attached.

There are mainly 2 type of nanoparticles :

There are mainly 2 type of nanoparticles MATRIX type RESERVIOR type Nanospheres - are solid core spherical particulates, which contain drug embedded within the matrix or adsorbed onto the surface.(Matrix type) Nanocapsules - are vesicular system in which drug is essentially encapsulated within the central core surronded by a polymeric sheath.(Reservoir type

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. NANOPARTICULATE CARRIERS NANOSHELLS DENDRIMERS QUANTUM DOTS CARBON NANOTUBES SOLID LIPID NANOPARTICLES LIPOSOMES NIOSOMES POLYMERIC NANOPARTICLES

Solid lipid nanoparticles:

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 ( drug or biologically active material ) is dissolved, entrapped, and or to which the active principle is adsorbed or attached. Nanoparticles are particles made of natural or synthetic polymers ranging in size from 50 to 500 nm. No potential toxicity problems as organic solvents are not used. Phospholipids monolayer

Advantages:

Advantages Small size & narrow size distribution provides for site specific drug delivery by SLNs Controlled release of active drug over a long period can be achieved Protection of incorporated drug against chemical degradation No toxic metabolites are produced Sterilization can be done by autoclaving or gamma irradiation Surface modification can be easily done

Disadvantages::

Disadvantages: Drug Loading capacity is limited High pressure induce drug degradation Coexistences of several colloidal species Lipid crystallization & drug incorporation - supercooled melts - gelation phenomenon Drug expulsion 10

Method of preparation::

Method of preparation : High pressure homogenization: Hot homogenization Cold homogenization Ultrasonication /high speed homogenization: Solvent emulsification/evaporation Micro emulsion based SLN preparations SLN preparation by using supercritical fluid Spray drying method 11

Hot homogenization:

Hot homogenization Melting of the lipid & dissolving/dispersing of the drug in the lipid Dispersing of the drug loaded lipid in a hot aqueous surfactant mixture. Premix using a stirrer to form a coarse preemulsion High pressure homogenization at a temperature above the lipid M.P. Hot O/W nanoemulsion Solid Lipid Nanoparticles Disadvantages: 1) temperature induce drug degradation 2) partioning effect 3) complexity of the crystallization 12

Cold homogenization:

Cold homogenization Melting of lipid & dissolving/dispersing of the drug in the lipid Solidification of the drug loaded lipid in liquid nitrogen or dry ice Grinding in a powder mill Dispersing the powder in a aqueous surfactant dispersion medium High pressure homogenization at room temperature or below. Solid Lipid Nanoparticles Disadvantages: 1) Larger particle sizes & broader size distribution 2) does not avoid thermal exposure but minimizes it 13

Ultrasonication/ high speed homogenization ::

Ultrasonication/ high speed homogenization : SLN were also developed by high speed stirring or sonication Adv. : 1) Equipment used is very common 2) No temperature induced drug degradation Disadv .: 1) Potential metal contamination 2) Broader particle size distribution ranging into micrometer range. 14

Solvent emulsification/ evaporation ::

Solvent emulsification/ evaporation : Lipophilic material is dissolved in a water immiscible organic solvent ( e.g.cyclohexane ) that is emulsified in an aqueous phase. Upon evaporation of solvent, a nanoparticle dispersion is formed by precipitation of lipid in aq. Medium. The mean diameter of the obtained particles was 25 nm with cholesterol acetate as model drug and lecithin/sodium glycocholate blend as emulsifier. Adv:- Avoidance of any thermal stress. Disadv:- use of organic solvents. 15

Micro emulsion based SLN preparations:

Micro emulsion based SLN preparations Preparation by stirring optically transparent mixture at 65-70 o c composed of a low melting fatty acid, emulsifier, coemulsifier & water. This hot microemulsion dispersed in cold water (2-3 o c) & stirring . By using Supercritical fluid Can be prepared by Rapid Expansion of Supercritical Carbon dioxide solution methods(RESS) Carbon dioxide with 99.99% is good solvent. Adv:- 1) Solvent less processing. 16

By Spray drying method:

By Spray drying method Alternative procedure to lyophilization in in order to transform an aqueous SLN dispersion into a drug product. Disadvantages:- 1) particle aggregation due to high temp., shear forces & partial melting of particles. 2) Recommended use of lipid with M.P. >70 0 c for spray drying. 17

Sterilization of SLNs:

Sterilization of SLNs For parentral & ocular administration SLNs must be sterile. For lecithin stabilized SLNs autoclaving is possible & it is not possible for sterically stabilized polymers. Physical stability during autoclave can not be stated, it depends on composition. SLN dispersion can also be sterilized by filtration. 18

Characterization of SLNs::

Characterization of SLNs: [I] Measurement of particle size Photon correlation spectroscopy Transmission electron microscopy Scanning electron microscopy [II] Measurement of Zeta Potential Allows predictions about the storage stability of colloidal dispersion Zeta potential under 30 mV are required for full electrostatic stabilization . 19

[III] Molecular weight :

[III] Molecular weight Gel chromatography Atomic force microscopy [IV] Surface element analysis X-ray photoelectron spectroscopy Electrophoresis Laser Doppler anaemometry [V] Density Helium compression pychnometry Contact angle measurement 20

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[VI] Molecular analysis H-NMR Infra red analysis [VI] Measurement of Crystallinity , Lipid modification DSC and X-ray scattering used to investigate status of lipid 21

APPLICATIONS:

APPLICATIONS Solid lipid Nanoparticles possesses a better stability and ease of up grad ability to production scale as compared to liposomes . SLNs form the basis of colloidal drug delivery systems, which are biodegradable and capable of being stored for at least one year . 22

SLNS AS COSMECEUTICALS:

SLNS AS COSMECEUTICALS Applied in the preparation of sunscreens. SLN has UV reflecting properties. ORAL SLN IN ANTITUBERCULAR THERAPY Anti-tubercular drugs such as rifampicin , isoniazide , loaded SLNs able to decrease dosing frequency and increase bioavailability. SLN AS A GENE VECTOR CARRIER Several recent reports of SLN carrying genetic materials such as DNA, plasmid DNA, & other nucleic acid have been reported. 23

References::

References: Vyas S.P. and Khar R.K. Targeted And Controlled Drug Delivery System, 1 st Edition, 2002, CBS Publication; 249 - 277. Jain N. K., Controlled and novel Drug Delivery, 1 st 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. 24

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Heurtault B., Saulnier P., Pech B., Proust J.E., Benoit J.P. “ Physico-chemical stability of colloidal lipid particles’’ Biomaterials 24 (2003) 4283-4300 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. 25

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26 Thank you