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classification,preparation,evaluation of nanoparticles

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  1. 1. SEMINAR ON NANOPARTICLESSUBMITTED TO:Dr.Hemanth Kumar YadavAsst ProfessorDept. of PharmaceuticsJSSCP,Mysore. PRESENTED BY:- Rajendra Prasad.P.C I Mpharm(IP) JSSCP
  2. 2. DEFINITION: “ Nanoparticles are sub-nanosized colloidal structures composed of synthetic or semi-synthetic polymers.” Size range : 10–1000 nm The drug is dissolved, entrapped, encapsulated or attached to a nanoparticle matrix.Based On Method Of Preparation:Nanocapsules:- Nanocapsules are systems in which the drug is confined to a cavity surrounded by a unique polymer membrane.Nanospheres:- Nanospheres are matrix systems in which the drug is physically and uniformly dispersed.
  3. 3. Nanoparticulate drug-delivery systems
  4. 4. Classificaton Of Nanoparticles: Solid Lipid Nanoparticles Polymeric Nanoparticles Ceramic Nanoparticles Hydrogel Nanoparticles Copolymerized Peptide Nanoparticles Nanocrystals and Nanosuspensions Nanotubes And Nanowires Functionalized Nanocarriers Nanospheres Nanocapsules
  5. 5.  Solid Lipid Nanoparticles:• New type of colloidal drug carrier system for i.v.• Consists of spherical solid lipid particles in the nm range, dispersed in water or in aqueous surfactant solution.Polymeric nanoparticles (PNPs) are defined as particulate dispersions or solid particles with size in the range of 10-1000nm.• Composed of synthetic or semi-synthetic Polymers. Biodegradable polymeric nanoparticles Polylactic acid (PLA), polyglycolic acid (PGA), Polylactic - glycolic acid (PLGA), and Polymethyl methacrylate (PMMA) Phospholipids Hydrophobic core
  6. 6. Ceramic Nanoparticles:• These are the nanoparticles made up of inorganic (ceramic) compounds silica, ( Inorganic/metal) titania and alumina. Exist in size less than 50 nm, which helps them in evading deeper parts of the body.Hydrogel nanoparticles:• Polymeric system involving the self-assembly and self aggregation of natural polymer amphiphiles cholesteroyl pullulan , cholesteroyl dextran and agarose cholesterol groups provide cross linking points.
  7. 7. Copolymerized Peptide Nanoparticles:• Drug moiety is covalently bound to the carrier instead of being physically entrapped. Nanocrystals And Nanosuspensions: Pure drug coated with surfactant, Aggregation of these particles in crystalline form .Drug powder dispersed in aqueous surfactant solution.Functionalized Nanocarriers• Biological materials like proteins, enzymes, peptides etc… are being utilized as a carriers for the drug delivery.
  8. 8. Advantages Of Nanoparticles:• Nano particle can be administered by parenteral, oral, nasal,occular routes.• By attaching specific ligands on to their surfaces,nano particles can be used for directing the drugs to specific target cells.• Improves stability and therapeutics index and reduce toxic affects.• Both active & passive drug targetting can be achieved by manipulating the particel size and surface characteristics of nano particles
  9. 9. Disadvantages Of Nanoparticles Small size & large surface area can lead to particle aggregation . Physical handling of nano particles is difficult in liquid and dry forms. Limited drug loading. Toxic metabolites may form.
  10. 10. Preparation of polymeric Nanoparticles Polymerization Preformed Super critical polymer fluid tech.Dispersion Emulsionpolymerization polymerization(DP) (EP) Solvent Solvent evaporation Displacement method method Salting outEP in an organic tech.continuousphase EP in aqueous Continuous phase
  11. 11. The selection of matrix materials is dependent on many factors including(a) size of nanoparticles required(b) inherent properties of the drug, e.g., aqueous solubilityand stability;(c) surface characteristics such as charge and permeability;(d) degree of biodegradability, biocompatibility and toxicity;(e) Drug release profile desired; and(f) Antigenicity of the final product.
  12. 12. Polymers For Nanoparticles Natural hydrophilic polymers• Proteins: - Gelatin, albumin, lectins, legumin.• Polysaccharides: - alginate, dextran, chitosan, agarose. Synthetic hydrophobic polymers• Pre-polymerized polymers: - Poly (e-caprolactone) (PECL),Poly (Lactic acid)(PLA), Polystyrene• Polymerized in process polymers: - Poly (isobutyl cyanoacrylates) (PICA), Poly (butyl cyano acrylates)
  13. 13. A. Nanoparticle Prepared By Polymerization Method Two approaches for preparation :1. Dispersion polymerization (DP): Used for preparation of biodegradable polyacrylamide & polymethyl methacrylate (PMMA). The acrylate or methyl methacrylate monomer is dissolved in aqueous phase. polymerization by γ-irradiation or chemical initiation combined with heating to tem. above 65 ˚c. The oligomer formed subsequently aggregate & above certain molecular weight precipitate in the form of nanoparticles
  14. 14. 2. Emulsion polymerization (EP): Monomer Dissolved in aqueous phase which contains an initiator which is a surfactant Vigorous agitation Emulsion formation Particle smaller than 100nm Initiator which generates either radicals or ions depending upon the type of initiator & these radicals or ions nucleate the monomeric unit & starts polymerization process.
  15. 15. 2.1)EP in an organic continuous phase:-Water solublemonomers are polymerized.Polyalkyl cynoacrylate (PACA) nanoparticles were preparedby EP in continuous organic phase. Drug dissolved in aq.phase Emulsified Organic solvent (hexane, chloroform)containing surfactant Microemulsion &monomer diffuse in swollen micelles OH¯ ions initiate polymerization Nanospheres
  16. 16. Preformed polymer:-1. Solvent evaporation method : Drug & polymer is dissolved in organic solvent. Emulsified with an aq. phase containing surfactant to obtain o/w emulsion. Organic phase is then evaporated Nanoparticles Example : polylactic acid nanoparticle loaded with testosterone using poloxamer 188 as stabilizer by using homogenizer.
  17. 17. 2. Solvent displacement / Nanoprecipitation : Drug dissolved in organic phase(ethanol/methanol) Emulsified Aq.phase Displacement of organic phase Immediate polymer precipitation because of complete miscibility of both the phase. Nanoparticles Useful for slightly water soluble drug.
  18. 18. 3. Salting out method : Suitable for drug & polymers that are soluble in polar solvent such as acetone or ethanol.
  19. 19. C. Super Critical Fluid Technology (SCF) :Advantages: Formation of dry nanoparticles. Rapid precipitation process. Contain very low traces of organic solvent. Involves use of environment friendly solvent like super critical carbon dioxide or nitrogen. SCF Technology Rapid Expansion of Super Critical Anti- Supercritical solution (RESS) solvent (SCA) For drugs soluble in SCF For drug insoluble in SCF
  20. 20. Rapid expansion of supercritical solution:• Drug dissolved in super critical fluid• Solution sprayed into region of low pressure.• Solvent power of super critical fluid decreases.• Precepitation of nanoparticles
  21. 21. Super Critical Anti-solvent (SCA) Drug + Methanol Drug is dissolved Add Super critical fluid (miscible with methanol)Precepitation of drug as fine particles
  22. 22. Equipments for Nanoparticles• Homogenizer• Ultra Sonicator• Mills• Spray Milling• Supercritical Fluid Technology• Electrospray• Ultracentrifugation• Nanofiltration
  23. 23. Homogenizer & Ultra Sonicator
  24. 24. Nano mill- Manufacturing Platform
  25. 25.  Evaluation of nanoparticles :1. Particle size2. Density3. Molecular weight4. Structure and crystallinity5. Specific surface area6. Surface charge & electronic mobility7. Surface hydrophobicity8. Invitro release9. Nanoparticle yield10. Drug entrapment efficiency
  26. 26. 1.Particle size : Photon correlation spectroscopy (PCS) : For smaller particle. Laser diffractrometry : For larger particle. Electron microscopy (EM) : Required coating of conductive material such as gold & limited to dry sample. Transmission electron microscopy (TEM) : Easier method & Permits differntiation among nanocapsule & nanoparticle. Atomic force microscope Laser force microscope Highresolution Scanning electron microscope microscope
  27. 27. 2.Density : Helium or air using a gas pycnometer Density gradiant centrifugation3. Molecular weight : Gel permeation chromatography using refractive index detector.4. Structure & Crystallinity : X-ray diffraction Thermoanalytical method such as, 1) Differential scanning calorimetry 2) Differential thermal analysis 3) Thermogravimetry
  28. 28. 5. Specific surface area : Sorptometer specific surface area A = 6 Density * diameter of particle6. Surface charge & electronic mobility : Surface charge of particle can be determined by measuring particle velocity in electrical field. Laser Doppler Anemometry tech. for determination of Nanoparticles velocities. Surface charge is also measured as electrical mobility. Charged composition critically decides bio-distribution of nanoparticle . Zeta potential can also be obtain by measuring the
  29. 29. electronic mobility.7. Surface Hydrophobicity : Important influence on intraction of nanoparticles with biological environment. Several methods have been used, 1. Hydrophobic interaction chromatography. 2. Two phase partition. 3. contact angle measurement.8. Invitro release : Diffusion cell Recently introduce modified Ultra-filtration tech. Media used : phosphate buffer9. Nanoparticle yield :% yield = Actual weight of product Total weight of excipient & Drug
  30. 30. 10. Drug entrapment efficiency :Drug entrapment % = Mass of drug in Nanoparticles 100 Mass of drug used in formulation
  31. 31. Applications
  32. 32. EMEND Rapamune (Merck & Co. Inc) (Wyeth-Ayerst Laboratories) ABRAXANE OLAY MOISTURIZERS(American Biosciences, Inc.) (Proctor and Gamble)
  33. 33. ConclusionNanoparticles are one of the novel drug delivery systems,which can be of potential use in controlling and targeting drugdelivery as well as in cosmetics textiles and paints. Judging bythe current interest and previous successes, nanoparticulatedrug delivery systems seems to be a viable and promisingstrategy for the biopharmaceutical industry.
  34. 34. References• Encyclopedia of controlled drug delivery system edited by Edith Mathiowitz, Pg. no:551-564.• Vyas S.P. , Khar R.K. Targeted & Controlled Drug Delivery, Novel Carrier Systems, CBS Publication ,2002 ,Page No.249- 277,331-387.• applications-field-pharmacy• Nanoparticles –A Review by VJ Mohanraj & Chen Y, Tropical Journal of Pharmaceutical Research 2006; 5(1): 561-573•• Jain N. K., Controlled and novel Drug Delivery, 1st edition 2001, CBS Publication; 292 - 301.
  35. 35. THANK YOU … …