Nanosuspension
Nanosuspension
Nanosuspension
INTRODUCTION
Definition
Nanosuspension can be defined as a biphasic
system consisting of pure drug particles
dispersed in a aqueous vehicle in which the
diameter of the suspended particle is less than
1m in size.
Nanosuspension consist of the poorly water soluble
compound without any matrix material suspended in
dispersion.
NANOSUSPENSION vs NANOPARTICLES
A pharmaceutical nanosuspension is defined as very
finely dispersed solid drug particles in an aqueous or
organic vehicle for either oral, topical, parenteral and
pulmonary administration.
The particle size distribution of the solid particles in
nanosuspensions is usually less than one micron with an
average particle size ranging between 200 and 600 nm.
Nanosuspensions differ from nanoparticles.
Nanoparticles are commonly polymeric colloidal carriers
of drugs whereas solid lipid nanoparticles are lipidic
carriers of drugs.
Advantages
Applicable to poorly water soluble as well as poorly
water and lipid soluble drugs.
Increased bioavailability
Increased saturation solubility due to larger surface area of
nanoparticles.
Increased dissolution raterelated to increased saturation solubility
according to Noyes-Whitney equation
Absorbed by endocytosis.
Adhesivenesscompared to microcrystal
Can be given by various routes of administration
I.V.route.
Useful in drug targetingpassive targeting.
Ease of manufacture and scale-up
Decrease in dose.
Decrease in food effect.
Stability Issues
Stability Issues
a. Deflocculate
d
b. Flocculated.
c. Nanosuspen
sion
Formulation
BOTTOM UP
TECHNOLOGY
NANOPRECIPITATI
ON
TOP DOWN
TECHNOLOGY
MEDIA
MILLING
High
pressure
homogeniza
tion in
water/
DISSOCUBES
High
pressure
homogeniza
tion in nonaqueous
solvent/
NANOPURE
NANOEDE
GE
1.Bottom up Technology
Bottom up Technology
In Bottom up technology the drug is
dissolved in a solvent, which is then
added to nonsolvent that causes
precipitation of the fine drug particles.
Simple and low expenditure.
In this technique, the drug needs to be
soluble in at least one solvent which is
miscible with nonsolvent.
PREPARATION TECHNIQUES
Bottom up Approach
Liquid Antisolvent Precipitation
Liquid Emulsion Technique
Sonoprecipitation
Preparation: sonoprecipiation
Drug is dissolved in organic solvent and
stabilizer, surfactants other ingredients is
dissolved in Aqueous solution.
Organic phase is added to aqueous phase then
sonicate for 5 second at 5 second interval for a
total of sonication time of 10 minutes.
Keep under vacuum for 1 hour to remove
organic solvent.[8]
Media Milling
The nanosuspensions are prepared by using high
shear media mills.
The milling chamber charged with milling media,
water, drug & stabilizer is rotated at very high shear
rate under controlled temp.
The milling medium is composed of glass, zirconium
oxide or highly cross-linked polystyrene resin.
The high energy shear forces are generated as a
result of impaction of milling media with the drug
resulting into breaking of microparticulate drug to
nanosized particles.
The major concern with this method is the residues
of milling media remaining in the finished product
Media Milling
In this method the nanosusensions are
produced using highshear media mills or
pearl mills.
Milling chamber consist of
1. Milling chamber
2. Milling shaft
3. Recirculation
4. Chamber
. Process is done under controlled
temperature.
Advantages
Drugs that are poorly soluble in both aqueous and
organic media can be easily formulated into
nanosuspensions.
Ease of scale-up and little batch-to-batch variation
Narrow size distribution of the nanoparticulate drug
present in the final product.
Allows aseptic production of nanosuspensions for
parenteral administration.
Flexibility in handling the drug quantity, ranging from
1 to 400mg/mL, thus enabling formulation of very
dilute as well as highly concentrated nanosuspensions.
Disadvantages
Preprocessing like micronization of drug is required.
Prerequisite of micronized drug particles.
Prerequisite of suspension formation using high-speed
mixers before subjecting it to homogenization.
High cost instruments are required that increases the cost of
Homogenisation In Nonaqueous
Media (Nanopure)
The drugs that are chemically labile can be
processed in such non-aqueous media or
water-miscible liquids like
polyethyleneglycol-400 (PEG), PEG1000
etc.
The homogenization can be done at room
temperature, 0o C and below freezing point
(-20o C).
Precipitate
d drug
particle
(nanosize)
Contineou
s to grow
till
microcrys
tal size
Nanoedege
Principle: same that of the
precipitation and homogenization
techniques.
In this technique the precipitated
suspension is further homogenized to
get smaller particle size and to avoid
crystal growth.
NON-solvent, such as methanol,
ethanol, and isopropanol added
Evaluation Parameters:
SEM, TEM
Atomic force microscopy
CHARACTERIZATION
Crystal
structure/ morphology:
Morphological evaluation of drug nanoparticles was
conducted through transmission electron microscopy
(TEM) and scanning electron microscopy (SEM).[9]
Application of
Nanosuspension
Bioavailability enhancement
Ocular administration
Intravenous administration
Pulmonary administration
Targeted drug deliver
Topical formulations
Application
Bioavailability enhancement:
Nanosuspensions resolve the problem of poor
bioavailability by solving problems of poor solubility
and poor permeability across the membrane.[12]
Application
Topical formulations:
Drug nanoparticles can be incorporated into creams and waterfree ointments.
The nanocrystalline form leads to an increased saturation
solubility of the drug in the topical dosage form, thus enhancing
the diffusion of the drug into the skin.[12]
Application
Parenteral administration:
Can be administered via different parenteral routes like intraarticular, intraperitoneal, intravenous injection.
For administration by the parenteral route, the drug either has to
be solubilized or has particle/globule size below 5 m to avoid
capillary blockage.
The current approaches for parenteral delivery include salt
formation, solubilization using co-solvents, micellar solutions,
complexation with cyclodextrin and recently liposomes.[12]
Oral administration:
Nanosizing of drugs can lead to a dramatic increase in their oral
absorption and subsequent bioavailability.[12]
COMPANY
PATENT/PATENT
APPLICATION
EXAMPLE
HODROSOL
NOVATIS(prev.sando
z)
GB 22 69 536
NANOMORPH
SOLIGS/ABBOTT
GB 22 00 048
D 1963 7517
NANOCRYSTAL
ELAN NANOSYSTEM
US 5,145, 684
DISSOCUBES
SKYPHARMA
US 5,858,410
NANOPURE
PHARMASOL
PCT/EPOO/0635
NANOEDGE
BAXTER
US 6,884,436
MARKETED NANOSUSPENSIONS:
PRODUCT
DRUG
COMPOUND
INDICATION
COMPANY
NANOPARTICE
TECHNOLOGY
RAPAMUNE
Sirolimus
Immunosuppre
sant
Wyeth
ELAN DRUG
DELIVARY
NANOCRYSTAL
EMEND
Aprepitant
Antiemetic
Merck
ELAN DRUG
DELIVARY
NANOCRYSTAL
TRICOR
Fenofibrate
Treatment of
hypercholester
olemia
Abbott
ELAN DRUG
DELIVARY
NANOCRYSTAL
MEGACEE
S
Megestrol
acetate
Appetite
stimulant
PAR
Pharmaceu
ticals
ELAN DRUG
DELIVARY
NANOCRYSTAL
TRIGLIDE
Fenofibrate
Treatment of
hypercholester
olemia
First
horizon
pharmaceu
ticals
SKYEPHARMA IDD
-P TECHNOLOGY
Conclusion:
Nanosuspension solved poor
bioavailability problem of hydrophobic
drugs and drugs which are poorly soluble
in aqueous and organic solutions.
Nanotechnique is simple, less
requirements of excipients, increased
dissolution velocity and saturation
solubility many poor bioavailability drugs
are formulated in nanosuspension form.
REFERENCES
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