SEMINAR ON

NANOPARTICLES

PRESENTED BY:-Rajendra Prasad.P.C

I Mpharm(IP)JSSCP

SUBMITTED TO:Dr.Hemanth Kumar YadavAsst ProfessorDept. of PharmaceuticsJSSCP,Mysore.

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.

Nanoparticulate drug-delivery systems

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

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

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.

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.

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

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.

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.

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 solubility and 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.

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)

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

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.

2.1)EP in an organic continuous phase:-Water soluble monomers are polymerized.

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

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.

2. Solvent displacement / Nanoprecipitation :

Useful for slightly water soluble drug.

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

3. Salting out method : Suitable for drug & polymers that are soluble in polar

solvent such as acetone or ethanol.

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

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

Super Critical Anti-solvent (SCA)

Drug + Methanol

Drug is dissolved

Add Super critical fluid (miscible with methanol)

Precepitation of drug as fine particles

Equipments for Nanoparticles

• Homogenizer• Ultra Sonicator• Mills• Spray Milling• Supercritical Fluid Technology• Electrospray• Ultracentrifugation• Nanofiltration

Homogenizer & Ultra Sonicator

Nano mill- Manufacturing Platform

Evaluation of nanoparticles :

1. Particle size

2. Density

3. Molecular weight

4. Structure and crystallinity

5. Specific surface area

6. Surface charge & electronic mobility

7. Surface hydrophobicity

8. Invitro release

9. Nanoparticle yield

10. Drug entrapment efficiency

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

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

5. Specific surface area : Sorptometer

specific surface area A = 6 Density * diameter of particle

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

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

10. Drug entrapment efficiency :Drug entrapment % = Mass of drug in Nanoparticles

Mass of drug used in formulation100

Applications

EMEND Rapamune

OLAY MOISTURIZERS

(Merck & Co. Inc) (Wyeth-Ayerst Laboratories)

(American Biosciences, Inc.) ABRAXANE

(Proctor and Gamble)

Conclusion Nanoparticles are one of the novel drug delivery systems, which can be of potential use in controlling and targeting drug delivery as well as in cosmetics textiles and paints. Judging by the current interest and previous successes, nanoparticulate drug delivery systems seems to be a viable and promising strategy for the biopharmaceutical industry.

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.

• www.pharmainfo.net/reviews/nanoparticles-and-its-applications-field-pharmacy

• Nanoparticles –A Review by VJ Mohanraj & Chen Y, Tropical Journal of Pharmaceutical Research 2006; 5(1): 561-573

• Google.com(images)• Jain N. K., Controlled and novel Drug Delivery, 1st edition

2001, CBS Publication; 292 - 301.

THANK YOU … …