nanoparticle ppt

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nanoparticles preparation & evaluation

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Presentation Transcript

NANOPARTICLE :

NANOPARTICLE Presented by: Mr. Chirag Patel Guided by: Mr. Ashok Barupal MAHARISHI ARVIND INSTITUTE OF PHARMACY MANSAROVAR, JAIPUR

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Definition: “ N anoparticles are sub- nanosized colloidal structures composed of synthetic or semi-synthetic polymers.” Size range : 1 – 1000 nm. Nanoparticles Nanocapsules Nanospheres Have core shell structure Represent matrix system

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Photographic View ( Nanoparticles ) :

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Preparation of polymeric Nanoparticles Dispersion polymerization (DP) Emulsion polymerization (EP) Solvent evaporation method Solvent Displacement method EP in aqueous Continuous phase EP in an organic continuous phase Salting out tech. Polymerization Preformed polymer Super critical fluid tech.

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Two approaches : The “ top-down ” approach, which involves the breaking down of large pieces of material to generate the required nanostructures from them. The “ bottom-up ” approach, which implies assembling single atoms and molecules into larger nanostructures . Top-down Bottom-up nanoparticles

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Nanoparticle prepared by polymerization method : Two approaches for preparation : 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

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Surfactant may or may not be used. PMMA nanoparticles used for vaccination purpose . The antigenic material is entrapped in nanoparticles using this tech. Emulsion polymerization (EP): Monomer is emulsified in non-solvent containing surfactant , which leads to formation of monomer micelles & stabilized monomer droplets. Initiator which generates either radicals or ions depending upon the type of initiator & these radicals or ions nucleate the monomeric unit & starts polymerization process. Being slightly soluble in surrounding phase , the monomer molecules reaches the micelles by diffusion from monomer droplets , thus allowing the polymerization process.

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2.1) EP in an organic continuous phase: Water soluble monomers are polymerized. Acrylamide & cross-linked N,N- bis acrylamide were prototype monomer to be polymerized using chemical initiator or by light irradiation , γ or UV radiation. Chemical initiator : N,N,N ̒ ,N ̒ – tetramethyl diamine & potassium peroxidisulfate . High toxicity of monomer & requirement of high amount of organic solvent and surfactant limits the importance of this process today. The cyanoacrylate monomers are relatively less toxic then acrylamine .

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Polyalkyl cynoacrylate (PACA) nanoparticles were prepared by EP in continuous organic phase. Drug dissolved in aq.phase Organic solvent (hexane, chloroform)containing surfactant Emulsified Microemulsion &monomer diffuse in swollen micelles OH¯ ions initiate polymerization Nanospheres

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2.2) EP In aqueous continuous phase: Very low quantity of surfactant. Monomer : alkyl cyanoacrylates Example : Polyethyl cyanoacrylate & polyisobutyl cyanoacrylate (PIBCA) containing metaclopramide nanoparticles . The cyanoacrylate monomer is initiated by OH ion & polymerization was performed at low pH to control the reaction otherwise leads to rapid polymerization. Stabilizer : poloxamer 188 = ↑ conc. ↓ particle size Example of DP & EP Nanoparticles : Polybutyl cyanoacrylate ( PBCA ) nanoparticle of n-butyl cyanoacrylate containing methotrexate were prepared by DP & EP method.

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DP Nanoparticles : Stabilizer : Dextran High release of methotrexate , due to channelizing effect of dextran chains incorporated in to nanoparticles during polymerization. EP Nanoparticles : Stabilizer : poloxamer 188 Comparatively less release of methotrexate . B. Nanoparticle prepared from pre-formed polymers: Hydrophilic polymer : Albumin , Gelatin , Alginate , chitosan . Hydrophobic polymer : poly(alkyl cyanoacrylates ) Polyesters: poly(lactic acid) , poly( glycolide ) ,

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poly( lactide -co-glycoside) ( PLGA ), poly( ε - caprolactone ). 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. Example : polylactic acid nanoparticle loaded with testosterone using poloxamer 188 as stabilizer by using homogenizer. The residual amount of stabilizer is required to be removed completely

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Incorporation of water soluble drug is limited in o/w emulsion method. Double emulsion (w/o/w ) solvent evaporation method : Organic solvent , polymer(PLGA) Aq. Phase,Stabilizer ,Drug (BSA) Sonication , Homogenization w/o emulsion Added to aq. phase with PVA W/O/W Emulsion Nanoparticles Organic solvent is evaporated

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2. Solvent displacement / Nanoprecipitation : Useful for slightly water soluble drug. However , loading efficincy of lipophilic drug such as indomethacin , betaxolol in nanoparticle of PLA , PLGA has been increased by using modified solvent displacement method. Drug dissolved in organic phase(ethanol/methanol) Aq.phase Displacement of organic phase Immediate polymer precipitation because of complete miscibility of both the phase. Nanoparticles Emulsified

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Modified method : 3. Salting out method : Method involves incorporation of acetone solution of polymer with drug in to saturated aq.solutions of PVA . Suitable for drug & polymers that are soluble in polar solvent such as acetone or ethanol. Aq.phase Distilled water , poloxamer 188 Organic phase Polar solvent, oil , polymer, drug Nanocapsules Magnetic stirring

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Miscibility of polymeric solution is in external aq.phase is prevented by saturation of external phase with PVA. Organic solvent (acetone),Drug polymer Distilled water, PVA Aq.phase Organic phase Nanoparticles O/W Emulsion Mechanical stirring Distilled water

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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 Supercritical solution (RESS) Super Critical Anti-solvent (SCA) For drugs soluble in SCF For drug insoluble in SCF

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Figure : Schematic of RESS process. 1. RESS Method : Disadvantages : Expansion zone Result in large particle due to aggregation. Many polymer exhibit little or no solubility in SCF. & polymer

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Figure : Schematic of SAS process. 2. SAS method : Anti-solvent High pressure & polymer Precipitation vessel Disadvantages : Result in large particle due to high viscosity of polymer-CO 2 solution. Poor Encapsulation . Inconsistency of particle size.

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Evaluation of nanoparticles : 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 Scanning electron microscope High resolution microscope

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2.Density : Helium or air using a gas pycnometer Density gradiant centrifugation 3. 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

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5. Specific surface area : Sorptometer 6. 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 Density * diameter of particle 6 specific surface area A =

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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 buffer 9. Nanoparticle yield : % yield = Actual weight of product Total weight of excipient & Drug * 100

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10. Drug entrapment efficiency : Drug entrapment % = Mass of drug in Nanoparticles Mass of drug used in formulation 100 *

Applications :

Applications Application Purpose Material Cancer therapy Targeting, Reduced toxicity, enhance uptake of anti-tumor agent Polyalkylcyanoacrylate with anticancer agent Intra cellular targeting Target reticuloendothelial system for intracellular infection Poly alkyl cyanoarylate Vaccine adjuvant Prolong systemic drug effect. Enhance immune response Poly methyl metha acrylate nanoparticles with vaccines DNA delivery Enhanced bioavailability and significantly higher expression level . DNA gelatin nanoparticles, DNA chitosan nanoparticles, Ocular delivery Improved retention of the drug and reduced washed out. Poly alkyl cyanoacrylate nanoparticles , anti-inflammatory agent

Reference :

Reference Gilbert SG, Christopher RT. Modern pharmaceutics. Fourth ed. Informa health care.1990. p. 269-271. Murthy RSR, Reddy H. Vesicular and particulate drug delivery system. 1 st ed. Career publication; Mar 2010. p. 231-263. Vyas S.P. , Khar R.K. Targeted & Controlled Drug Delivery, Novel Carrier Systems, CBS Publication ,2002 ,Page No.331-387. www.pharmainfo.net www.sciencedirect.com

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THANK YOU … …