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POLYMERIC NANOPARTICLES-
A NOVEL APPROACH
Prepared by: Shivam Thakore Guided by: Ms Rudree Pathak Ankit Patel
05/03/2023 1Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad
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Table of Contents Introduction Advantages Disadvantages Polymers used Method Of Preparation Characterization Questions that can be asked References
05/03/2023 2Department of Pharmaceutical Technology, LJ
institute of Pharmacy, Ahmedabad
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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
05/03/2023 3Department of Pharmaceutical Technology, LJ
institute of Pharmacy, Ahmedabad
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Depending upon Method
of Preparati
on
Nanospheres
Nanocapsules
05/03/2023 4Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad
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05/03/2023 5Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad
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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.
05/03/2023 6Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad
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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.
05/03/2023 7Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad
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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
05/03/2023 8Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad
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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.
05/03/2023 9Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad
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Polymers used in Preparation
Natural Hydrophilic
Proteins
Polysaccharides05/03/2023 10
Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad
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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)
05/03/2023 11Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad
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Method of Preparation
05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 12
Polymerization based methods
Polymer precipitation
methods
Amphiphilic
macromolecule cross-
linking
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05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 13
Heat Cross-linking
Chemical Cross-linking
Amphiphilic macromolecule
cross-linking
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05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 14
Polymerization based Methods
Polymerization of monomers Emulsion
polymerization
Interfacial complexat
ion
Dispersion polymerization
Interfacial condensation polymerization
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05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 15
PolymerPrecipitation
methods
Solvent extraction/
evaporation
Solvent displacement
(nanoprecipitation)
Salting out
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05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 16
Amphiphilic Macromolecule cross-linking
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Heat / Chemical Cross-Linking
05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 17
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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05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 18
PolymerPrecipitation
methods
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Solvent extraction method(SEM) Single emulsion
05/03/2023Department of Pharmaceutical Technology,
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Organic phase,
Solvent, Drug,
Polymer
Aqueous phase,
Distilled water, stabilizer
Sonication, homogenizaion
O/W emulsion
Oil droplet
Solvent evaporation
Nanoparticles obtained
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Double Emulsion SEM
05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 20
Organic phase,
solvent, drug, polymer
Aqueous Phase, Water,
Stabilizer
Sonication, homogenization
W/O emulsion
stablized at 4 C
W/O/W emulsion
Nano particles
Aq phase with stabilizer(PVA)
Solvent evaporation
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Solvent Displacement (Nanoprecipitation)
05/03/2023Department of Pharmaceutical Technology,
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Aq phase Distilled water,
Poloxamer 188
Organic phase, Organic solvent, Polymer, drug
Nano spheres
Aq phaseDistilled Water,
Poloxamer 188
Organic phase,Polar solvent, Oil, Polymer,
Drug
Nano capsules
Magnetic stirring
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Salting Out
05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 22
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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05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 23
Polymerization Based methods
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Emulsion Polymerization It may be conventional or reverse, depending
upon nature of continuous phase,Conventional method= Aq phase in ContinuousReverse method= Organic is continuous phase
05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 24
Monomer is emulsified in non-solvent partially soluble phase with stabilizer, leading to formation of monomer swollen micelles
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05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 25
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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05/03/2023Department of Pharmaceutical Technology,
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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.
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Be careful while using Chemical initiator
05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 27
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 orPotassium Peroxodisulfate
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Dispersion polymerization
05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 28
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
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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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05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 30
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
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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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LJ institute of Pharmacy, Ahmedabad 33
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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 usedDSCDTATGA
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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.
05/03/2023Department of Pharmaceutical Technology,
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Applications in some areas of medicine Corticoids release Anticancer therapy Crossing BBB Vaccines and gene therapy Diagnostic Ocular delivery
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LJ institute of Pharmacy, Ahmedabad 37
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LJ institute of Pharmacy, Ahmedabad 38
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Products in PipelineCompany Technology API Route of
administrationNovavax, USA Micellar
nanoparticlesTestosterone S.c.
BioAUiance, France Polydsohexylcyanoacrylate)nanoparticles
Doxorubicin i.v.
AmericanBioscience, USA
Albumin-Drugnanoparticles
Paclitaxel i.v.
Wyeth Pharmaceutical, USA
Drug Nanoparticles Rapamycin Oral
BioSante, USA Calcium phospahtenanoparticles
Insulin Oral
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LJ institute of Pharmacy, Ahmedabad 39
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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
05/03/2023 40Department of Pharmaceutical Technology,
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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
05/03/2023Department of Pharmaceutical Technology,
LJ institute of Pharmacy, Ahmedabad 41
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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
05/03/2023 42Department of Pharmaceutical Technology,
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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
05/03/2023 43Department of Pharmaceutical Technology,
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Khar RK and Vyas SP, “Targetted and controlledd drug delivery”
Torchilin p v, “nanoparticulates drug carriers”, imperial college press, london
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LJ institute of Pharmacy, Ahmedabad 44
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Thanks for attention,LJIP, Ahmedabad
05/03/2023 45Department of Pharmaceutical Technology,
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