Polymeric nanoparticles A Novel Approach

Prepared by: Shivam Thakore Guided by: Ms Rudree Pathak
Ankit Patel
7/26/2013 1
Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad

Table of Contents
 Introduction
 Advantages
 Disadvantages
 Polymers used
 Method Of Preparation
 Characterization
 Questions that can be asked
 References
7/26/2013 2
Department of Pharmaceutical Technology, LJ
institute of Pharmacy, Ahmedabad

Introduction: Polymeric
Nanoparticles
• What are PNP’s?
○ They are solid colloidal particles ranging in size from
10 to 1000 nm (1µm).
 Drug may be dissolved, entrapped, encapsulated or
attached to a nanoparticle matrix .
 Because these systems have very high surface
areas, drugs may also be adsorbed on their surface.
 Polymer-based nanoparticles effectively carry
drugs, proteins and DNA to target cells and organs.
 Their nanometer-size promotes effective permeation
through cell membranes and stability in the blood
stream
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Department of Pharmaceutical Technology, LJ
institute of Pharmacy, Ahmedabad

Depending upon
Method of
Preparation
Nanospheres Nanocapsules
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 Nanocapsules: They are the systems in which the drug is
confined to a cavity surrounded by a unique polymer
membrane.
 Nanospheres: They are the matrix systems in which the
drug is physically and uniformly dispersed.
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Advantages
 Increases the stability of any volatile agents & can be
easily and cheaply fabricated in large quantities by a
multimethods.
 Has significant advantages over traditional oral and
intravenous methods of administration in terms of
efficiency and effectiveness.
 Delivers a higher concentration of pharmaceutical
agent.
 The choice of polymer and the ability to modify drug
release from polymeric nanoparticles have made them
ideal candidates for cancer therapy, delivery of
vaccines, contraceptives and delivery of targeted
antibiotics.
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Cont…
 Targeted Drug Delivery System.
 Polymeric nanoparticles can be easily incorporated into
other activities related to drug delivery, such as tissue
engineering
 Other all advantages over single unit dosage forms are
as such
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Disadvantages
 Very costly formulation with no low yield
 Productivity is more difficult. As a industrial
applications, Technology transfer to commercial
production is very difficult.
 Reduced ability to adjust the dose
 Highly sophisticated technology
 Requires skills to manufacture.
 Stability of dosage form is big issue owing to its nano
size.
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Polymers used in Preparation
Natural
Hydrophilic
Proteins
Polysaccharides
Synthetic
Hydrophobic
Pre-Polymerized
Polymerized in
process
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PROTIENS POLYSACHCHARIDES
Gelatin Alginate
Albumin Dextran
Lectin Chitosan
Legumine Agarose
Viciline Pullulan
PRE-POLYMERIZED POLYMERIZED IN PROCESS
Poly E caprolactone Poly Isobutyrl cyano acrylates (PICA
PLA PBCA
Poly lactide co glycolide (PLGA) PHCA
Polystyrene Poly methyl methacyrlate (PMMA)
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Method of Preparation
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LJ institute of Pharmacy, Ahmedabad 12
Polymerization
based
methods
Polymer
precipitation
methods
Amphiphilic
macromolecul
e cross-linking

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Heat Cross-
linking
Chemical
Cross-
linking
Amphiphilic
macromolecule
cross-linking

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Polymerization
based Methods
Polymerization
of monomers
Emulsion
polymeriza
tion
Interfacial
complexat
ion
Dispersion
polymerization
Interfacial
condensation
polymerization

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Polymer
Precipitation
methods
Solvent
extraction/
evaporation
Solvent
displacement
(nanoprecipitation)
Salting out

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Heat / Chemical Cross-Linking
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Aq protein
(BSA),
Surfactant
Oil
High Pressure
Homoginization
W/O
emulsion
Centrifugation & isolation
of nanoparticles
Dilution with preheated oil
{Heat CL} or Add cross-linking
agent {chemical CL}

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Solvent extraction method(SEM)
Single emulsion
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Organic
phase,
Solvent,
Drug,
Polymer
Aqueous
phase, Distille
d
water, stabiliz
er
Sonication, homo
genizaion
O/W
emulsion
Oil
droplet
Solvent
evaporation
Nano
particles
obtained

Double Emulsion SEM
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Organic
phase,
solvent, drug,
polymer
Aqueous
Phase, Water,
Stabilizer
Sonication, homo
genization
W/O
emulsion
stablized at
4 C
W/O/W
emulsion
Nano
particles
Aq phase with
stabilizer(PVA)
Solvent
evaporation

Solvent Displacement
(Nanoprecipitation)
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Aq phase
Distilled water,
Poloxamer
188
Organic phase, Organic
solvent, Polymer, drug
Nano
spheres
Aq phase
Distilled
Water, Poloxa
mer 188
Organic phase,
Polar
solvent, Oil, Polymer, Drug
Nano
capsules
Magnetic
stirring

Salting Out
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Org phase.
Org solvent,
Drug,
Polymer
Aq
phase, dist
water, PVA,
MgCl2
Mechanical
Stirring
O/W
emulsion
Nano
spheres
Dist Water

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Emulsion Polymerization
 It may be conventional or reverse, depending
upon nature of continuous phase,
 Conventional method= Aq phase in Continuous
 Reverse method= Organic is continuous phase
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Monomer is emulsified in non-solvent partially soluble phase with
stabilizer, leading to formation of monomer swollen micelles

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Polymerization takes place in presence of intiator (chemical/physical), which
provides energy to monomer, So that in becomes Free Reactive radical
It collides with the surrounding unnreactive monomers, and initiates the
POLYMERIZATiON reaction.
It continues till concentration of monomer/intiator is consumed
Mechanism is micellar polymerization were Swollen monomer micelles act as a
site of nucleation & polymerization

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As monomer is slightly soluble in surrounding phase, it diffuses from monomer
droplets and reach monomer micelles through continuous phase.
Thus polymerization takes places in MICELLES.

Be careful while using Chemical initiator
7/26/2013
Flush the Aq medium
with nitrogen gas for
1hr to remove
completely oxygen
from it.
Interferes the radical
polymerization
process, Apart from that
it forms O radical & We
already know HOW
HARMFUL THEY ARE!!!!
Ammonium or
Potassium Peroxodisulfate

Dispersion polymerization
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Here, monomer instead of being dispersed, is dissolved in the Aq
medium, which act as a precipitant for formed polymer.
Nucleation is directly induced in Aq. Monomer solution.
So STABILIZER/ SURFACTANT is no needed
Initiation here is achieved by different mechanism, but mostly it is by irradiating
solution with high energy radiation (g, UV, strong visible light).
PROCESS GOES AS EMULSION POLYMERIZATION

Interfacial condensation
Polymerization
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It involves step polymerization of two different monomers, dissolved in two
phases respectively, Continuous and Dispersed phase.
Polymerization reaction takes place at the interfaces of two liquids.
Nanometre-sized hollow polymer particles were synthesized by employing
interfacial cross-linking reactions as polyaddition and polycondensation or
radical polymerization.

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Oil-containing nanocapsules were obtained by the polymerization of monomers
at the oil/water interface of a very fine oil-in-water micro- emulsion. The organic
solvent, which was completely miscible with water, served as a monomer vehicle
and the interfacial polymerization of the monomer was believed to occur at the
surface of the oil droplets that formed during emulsification
Reverse is the case with preparation of water containing Nanocapusles

Characterization of PNP’s
 Particle size and size distribution
 Surface area, surface chemistry, surface coating and
porosity
 Hydrophilicity and surface charge density
 Purity and quality
 Stability (on shelf and upon administration)
 Drug release parameters and bioequivalence testing
considerations
 % Entrapment efficiency
 % PNP Yield
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Size evaluation
 Done by number of methods with/without Freeze
fracture like
 Photon correlation spectroscopy,
 Transmission electron microscopy(TEM)
 Scanning electron microscopy(SEM)
 The spherical shape of the nanocapsules was
confirmed by atomic force microscopy
 At present, TEM is most successfully used in
determining the nanocap structure, polymer
envelope and the inner cavity & allowing the wall
thickness to be estimated.
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 Laser Difractometry : For larger particles
 Freeze fracture has also allowed the visualization of different
possible organizations of lipophilic surfactant, which can form
vesicles,
micelles,
Bilayers,
Monolayers,
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Surface Charge, Molecular
Wt, Structure & Crystallinility
 Surface Charge: Measuring particle velocity in
electric field
 Molecule charge: Gel permeation
 For Structure/crystallinity different thermal
methods are used
 DSC
 DTA
 TGA
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Purity, % EE, % Yield
 Purity & Quality: Assay of PNP with suitable estimation
techniques.
 % Entrapement Efficency:
 % Yield:
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In vitro Drug release
 Ideally Franz-diffusion cell is used, but is not appropriate for
nano/multiparticulate DDS.
 Hence, generally, Cellophane bag filled with the product is
used, that is dipped suitable in the beaker filled with proper
media, aliquots are taken at regular time intervals.
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Applications in some areas of
medicine
 Corticoids release
 Anticancer therapy
 Crossing BBB
 Vaccines and gene therapy
 Diagnostic
 Ocular delivery
7/26/2013

7/26/2013

Products in Pipeline
Company Technology API Route of
administration
Novavax, USA Micellar
nanoparticles
Testosterone S.c.
BioAUiance, France Polydsohexyl
cyanoacrylate)
nanoparticles
Doxorubicin i.v.
American
Bioscience, USA
Albumin-Drug
nanoparticles
Paclitaxel i.v.
Wyeth
Pharmaceutical,
USA
Drug Nanoparticles Rapamycin Oral
BioSante, USA Calcium phospahte
nanoparticles
Insulin Oral
7/26/2013

Question to Crack GTU
 Define nanotechnology and various products prepared by it.
Explain application of nanoparticles and nanosuspensions giving
examples for their market products. 5M JAN 2011
 Briefly introduce the term nanotechnology. Enlist the commonly
used polymers into these products. Discuss any one method of
preparation of nanoparticle. 6M JUNE 2011
 Write about applications of nanoparticulate drug delivery system.
5M JUNE 2011
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 Explain the terms Nanotechnology and Nanoparticles.
Enumerate different parameters and characterization
methods for each parameter in context to
characterization of Nanoparticulate system.
8M MAY 2012
 Nanotechnology and its applications
5M NOV 2012
 Give application of nanotechnology in the field of
pharmaceutical science 5M DEC 2011
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References
 Kumari A, Yadav S, Yadav SC, “Biodegradable polymeric
nanoparticles based drug delivery systems”,Colloids
and Surfaces B: Biointerfaces , elsevier.com, 2010, vol
75 Pg:1–18
 Nagavarma BVN, Yadav HKS*, Ayaz A, Vasudha LS,
Shivakumar HG. “Different techniques for preparation
of polymeric nanoparticles- a review ”, Asian J Pharm
Clin Res, Vol 5, Suppl 3, 2012, Pg.16-23
 Jain N.K. “Advances in controlled and novel Drug
Delivery”, CBS publisher & Distributers, Edition 1st
2001, Pg. 408
7/26/2013 42

 Zhang G, Niu A, Peng S, Jiang M, Tu Y, Li M, Wu C,
“Formation of Novel Polymeric Nanoparticles”, vol. 34,
no. 3, 2001 / accounts of chemical research, pg .249-
256
 Kreuter J, “Nanoparticles—a historical perspective”,
International Journal of Pharmaceutics, vol 331 (2007)
elsevier.com,Pg. 1–10
 Cismaru L, Popa M,” polymeric nanoparticles with
biomedical applications”, Rev. Roum. Chim., vol 55(8)
2010, Pg 433-442
7/26/2013 43

 Khar RK and Vyas SP, “Targetted and controlledd drug
delivery”
 Torchilin p v, “nanoparticulates drug carriers”, imperial
college press, london
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Polymeric nanoparticles A Novel Approach

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