4. ORIGIN
The prefix “Nano” is a
Greek word which means
“dwarf ”, very small or
miniature size[1]
‘Nanotechnology, also shortened to nanotech, is the use of
matter on an atomic, molecular, and supramolecular scale
for industrial purposes.]
NANOTECHNOLOGY
‘Pharmaceutical nanotechnology’ embraces applications
of nanoscience to pharmacy as nanomaterials, and as
devices like drug delivery,diagnostic, imaging and
biosensor[3]
PHARMACEUTICAL
NANOTECHNOLOGY
Nanoparticles are solid colloidal particles consisting of
macromolecular substances that vary in size from 10nm
to 1,000 nm[4]
NANOPARTICLES
8. DEFINITION
The polymeric nanoparticles are prepared from
biocompatible and biodegradable polymers in
size between 10-1000 nm where the drug is
dissolved, entrapped, encapsulated or attached
to a nanoparticle matrix.[6]
Depending upon the method of
preparation nanoparticles, nanospheres or
nanocapsules can be obtained.
Nanocapsules are systems in which the
drug is confined to a cavity surrounded by a
unique polymer membrane.
Nanospheres are matrix systems in which
the drug is physically and uniformly
dispersed.
Polymers are very convenient materials for
the manufacture of countless and varied
molecular designs that can be integrated
into unique nanoparticle constructs with
many potential medical applications.[4]
10. 1 2 3
4 5 6
There are Various routes of
administration available, like
oral, nasal, parenteral[9]
Improvement over traditional
oral and IV methods of
administration in terms of
efficiency & effectiveness[8]
Delivers a desired concentration
of pharmaceutical agent to a
desired location[6]
Stable dosage forms of drug
which are either unstable or
have low bioavailability can be
formulated[8]
ADVANTAGES
7 8 9
Because of their small size, can
penetrate through smaller
capillaries & are taken up by
cells[8]
Increasing the resistance time
in the body (increasing the
half-life for the clearance)[8]
Improving drug bioavailability
through enhancing aqueous
solubility[8]
Minimizes non-specific uptake,
prevents undesirable off target
and side effects[8]
PNPs can be easily
incorporated into other
activities related to drug
delivery, such as tissue
engineering[6]
11. 02
High cost
High sophisticated
technology
01
Their small size and large
surface area can lead to
particle aggregation,
making physical handling
of NPs difficult in liquid
and dry forms[8]
03
diffusion and biodegradation govern the
process of drug release. In most cases, rapid
drug release from polymer nanoparticles,
called “ burst release”, can be observed
initially. It is reported that the release profiles
of the drugs from polymer nanoparticles
depend upon the nature of the delivery
system.
DISADVANTAGES
12. Polymer are large or macromolecule containing several small repeating units.
These are formed from small macromolecules called monomers through a process known
as polymerization .
DEFINITION
POLYMERS
Easy to sythesise Non immunogenic
Biocompatible Non toxic
Inexpensive
Biodegradable
14. PREPARATION
DISPERSION OF
PREFORMED POLYMER
POLYMERIZATION
OF MONOMERS
IONIC GELATION
a) Solvent evaporation
b) Nanoprecipitation
c) Salting out
d) Dialysis
e) Supercritical fluid
technology
Mini emulsion
( Coacervation of
hydrophilic polymers )
15. SOLVENT EVAPORATION
Fig.2 Schematic representation of the solvent evaporation method[7]
SONICATION
EVAPORATION
PURIFICATION
Surfactant
Drug
Polymers
1) Suitable thermolabile drugs
2) Small particle size
ADVANTAGES
DISADVANTAGES
1) Presence of solvent residues
in the final dispersion may
create problems
16. NANOPRECITATION
1) Simple and rapid preparation
2) Suited for most of the poorly
soluble drugs
ADVANTAGES
DISADVANTAGES
1) Particle size is affected by
rates of addition of the
organic phase into the
aqueous phase
SOLVENT
EVAPORATION
Precipitation of polymer
Polymeric nanoparticles
Surfactant
Drug
Polymers
Fig.3 Schematic representation of the nanoprecipitation method[7]
17. SALTING OUT
1) Useful for heat sensitive
substances
ADVANTAGES
DISADVANTAGES
1) Extensive nanoparticle
washing steps.
EMULSIFICATION EVAPORATION
Fig.5 Schematic representation of the salting out method[7]
18. DIALYSIS
1) Simple and effective method
ADVANTAGES
DISADVANTAGES
1) Solvent used in the
preparation of the polymer
solution affects the
morphology and particle
size distribution
DIALYSIS
Fig.6 Schematic representation of the dialysis method[7]
Polymer and the drug is dissolved in a organic solvent
▪ This solution is added to dialysis tube and dialysis performed against
a non solvent miscible with the former miscible.
▪ The displacement of the solvent inside the membrane is followed by
the progressive aggregation of polymer due to loss of solubility and
formation of homogenous suspension of nanoparticles.
19. SUPERCRITICAL FLUID TECHNOLOGY
(SCF)
Fig.7 Schematic representation of the RESS method[6]
The solute is dissolved in a
supercritical fluid to form a
solution. followed by the rapid
expansion of the solution across
an orifice or a capillary nozzle into
ambient air.
The high degree of super
saturation, accompanied by the
rapid pressure reduction in the
expansion, result in homogenous
nucleation and thereby, the
formation of well-dispersed
particles.
Results from mechanistic studies
of different model solutes for the
RESS process indicate that both
nanometer and micrometer-sized
particles.
Drug
dissolved in
super critical
fluid
Solution
sprayed into
region of low
pressure
Solvent power
of super
critical fluid
decreases
Precipitation
of
nanoparticles
20. EMULSION POLYMERIZATION
1) Fastest method
2) Readily scalable
ADVANTAGES
DISADVANTAGES
1) It requires toxic organic
solvents, surfactants,
monomers, and initiator,
which are subsequently
eliminated from the formed.
Oil , drug, monomer,
stabilizer (lecithin) Aqueous phase(Polaxomer)
O/W emulsion
Isolation of
Nanoparticles
21. MINI EMULSION POLYMERIZATION
Surfctant micelle with
monomer in core
Surfctant micelle
with polymer in core
Fig.9 Schematic representation of miniemulsion polymerization process[11]
22. IONIC GELATION
Fig.10 Schematic Representation of the ion gelation method[6]
The method involves a mixture of two aqueous phases, of which one is the polymer chitosan, a di-block co-polymer
ethylene oxide or propylene oxide (PEO-PPO) and the other is a poly anion sodium tripolyphosphate.[6]
In this method, positively charged amino group of chitosan interacts with negative charged tripolyphosphate to form
coacervates with a size in the range of nanometer.[6]
chitosan + Drug
solution
Drug loaded
nanopartciles
HIGH SPEED
HOMOGENIZATION
sodium
tripolyphosphate.
23. TREATMENT
1) Evaporation under
reduced pressure
2) Centrifugation&
Ultracentrifugation
3) Filtration through
mesh or filter
4) Dialysis
5) Gel filtration
PURIFICATION STERILIZARTION DRYING CONCENTRATING
1) Autoclaving
2) Gamma irradiation
3) Membrane filtration
4) High hydrostatic
pressure sterilization
5) Using ethylene oxide
or formaldehyde
microbiological conta-
mination, Hydrolysis,
Physicochemical instability
1) Freeze-drying
2) Spray-drying
processes
1) Dried preparations
obtained either by
freeze drying or spray
drying can be
reconstituted
2) ultracentrifugation
can be redispersed in
a smaller volume
24. EVALUATIONS
01
PARTICAL SIZE &
MORPHOLOGY
Measurement techniques:
1) Dynamic light scattering (DLS)
2) Scanning electron microscopy
3) Transmission electron microscope
4) Atomic force microscopy (AFM)
02
MOLAR MASS
DISTRIBUTION OF
THE POLYMER
Measurement techniques:[7]
1) Size-exclusion chromatography
(SEC)
2) Static light scattering (SLS)
03
SURFACE
CHARGE
The measurement of the zeta
potential allows for predictions
about the storage stability of
colloidal dispersion.
04
SURFACE
HYDROPHOBICITY
Measurement techniques:[9]
1) Hydrophobic interaction
chromatography,
2) Biphasic partitioning
3) Contact angle measurements
05
The specific surface area of freeze
dried nanoparticles is generally
determined with the help of
sorptometer.[38]
SPECIFIC SURFACE
AREA
06
% E.E[8] =
Total drug added - unentrapped drug ×100
Total drug added
25. APPLICATIONS
CANCER THERAPY INTRACELLULAR
TRARGETING
BRAIN
DELIVERY
VACCINE ADJUVENT
Poly
(alkylcyanoacrylate)
NPs with anticancer
agents like,
Doxorubicin,
Acyclovir
Poly(alkyl
cyanoacrylate)poly
esters
nanoparticles with
anti parasitic or
antiviral agents
Poly (methyl
methacrylate)
nanoparticles with
vaccines (oral and IM
immunisation)
Drugs successfully
benn used for brain
targeting are
Tubocurarine,
doxorubixine
27. MARKETED PRODUCTS
CIMZIA®
(certolizumab pegol)
Adagen®
Pegademase bovine
Cimzia is used for treatment of
patients with rheumatoid arthritis,
Crohn’s disease, psoriatic arthritis
and ankylosing spondylitis[39]
PEGylated adenosine deaminase
(ADA) which gained FDA approval in
1990. Approval of Adagen was only
based on the results with 12 patients,
which gives this drug ‘orphan disease
status’[39]
It is used for the treatment of
febrile neutropenia. The half-life of
the native molecule (filgrastim) is
about 3.5–3.8 h, but Neulasta remains
in circulation up to 42 h.[39]
Neulasta®
(PEGfilgrastim)
30. SLN are sub-micron colloidal carriers ranging from 10 to 1000 nm, composed of
physiological lipid dispersed in water or in aqueous surfactant solution.
SLNs introduced in 1991 represent an alternative and better carrier system to
traditional colloidal carriers such as emulsions, liposomes and polymeric micro
and nanoparticles.[42]
DEFINITION
Fig.11 Schematic presentation of the complete structure of solid lipid nanoparticles[44]
38. SUPER CRITICAL FLUID TECHNIQUE
Drug dissolved in super critical fluid
Solution sprayed into region of low pressure
Solvent power of super critical fluid decreases
Precipitation of nanoparticles
Advantages:
Formation of dry
nanoparticles
Rapid precipitation process.
Contain very low traces of
organic solvent.
Involves use of environment
friendly solvent like SC
carbon dioxide or nitrogen.
40. Protective properties of SLN for
chemically labile drugs against
degradation and the occlusion effect
due to film formation on the skin.
TOPICAL APPLICATION
It could be shown for nanoparticles that
an increased adhesiveness is available
leading to higher drug levels at desired
site of action
OPHTHALMIC
ADMINISTRATION
simple approach is the aerosolization of
aqueous SLN dispersions.
PULMONARY
ADMINISTRATION
It include aqueous dispersions or SLN
loaded traditional dosage forms.
e.g. tablets, pellets or capsules.
PER ORAL
ADMINISTRATION
Pharmacokinetic studies of
doxorubicin incorporated into SLN
showed higher blood levels after i.v.
injection in rats.
PARENTERAL
ADMINISTRATION
An increase of the solid lipid content of
the SLN dispersion results in semisolid,
gel-like systems, Acceptable for direct
application on the skin.
TRANSDERMAL
ADMINISTRATION
APPLICATIONS
01
02
03
04
05
06
41. MARKETED PRODUCTS
MUCOSOLVAN RETARD
(Ambroxol)
Mucosolvan retard capsules was the first generation.
It was produced by highspeed stirring of amelted lipid
phase in a hot surfactant solution obtaining an
emulsion. This emulsion was then cooled down to
room temperature obtaining the so-called “lipid
nanopellets for oral administration”
41
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