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 Introduction of Nanoparticles
 Solid lipid Nanoparticles
 Advantage & disadvantages of SLNs
 Methods of Preparation
 Sterilization Criteria
 Characterization of SLNs
 Applications of SLNs
 References
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.
   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 : Consists of polymer wall
    entrapping an oily core in which the drug is
    dissolved
         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.
MATRIX         RESERVIOR
               type            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
POLYMERIC
                NANOPARTICLES
LIPOSOMES                         QUANTUM
                                  DOTS




                NANOPARTICULATE
DENDRIMERS                            NIOSOMES
                   CARRIERS




 SOLID LIPID                        NANOSHELLS
NANOPARTICLES      CARBON
                  NANOTUBES
 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
 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
 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
 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
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
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
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
 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
 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 (2-3oc) &
  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
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. >700 c for spray
    drying.




                                                                   17
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
[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
 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
[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
 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
 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
 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, 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
 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
Thank you

            26

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Nanoparticles

  • 1.
  • 2.  Introduction of Nanoparticles  Solid lipid Nanoparticles  Advantage & disadvantages of SLNs  Methods of Preparation  Sterilization Criteria  Characterization of SLNs  Applications of SLNs  References
  • 3. 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.
  • 4. 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 : Consists of polymer wall entrapping an oily core in which the drug is dissolved
  • 5. 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.
  • 6. MATRIX RESERVIOR type 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
  • 7. POLYMERIC NANOPARTICLES LIPOSOMES QUANTUM DOTS NANOPARTICULATE DENDRIMERS NIOSOMES CARRIERS SOLID LIPID NANOSHELLS NANOPARTICLES CARBON NANOTUBES
  • 8.  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
  • 9.  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
  • 10.  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
  • 11.  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
  • 12. 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
  • 13. 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
  • 14. 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
  • 15.  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
  • 16.  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 (2-3oc) & 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
  • 17. 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. >700 c for spray drying. 17
  • 18. 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
  • 19. [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
  • 20.  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
  • 21. [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
  • 22.  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
  • 23.  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
  • 24.  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, 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
  • 25.  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
  • 26. Thank you 26