1. Prepared by
Guided by:
MAYURI B .YADAV
PROF. Dr. S. N. DHOLE
FIRST SEMESTER, M.PHARM,
ASSO. PROFFESOR
DEPT OF PHARMACEUTICS
DEPT OF PHARMACEUTICS
Modern College Of Pharmacy (For Ladies), Moshi, Pune
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2. CONTENTS…..
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Introduction
Formulation
Properties Of Nanosuspensions
Method Of Preparation
Evaluation Parameter
Current Marketed Formulation
Literature Survey
Pharmaceutical Applications
Conclusion
References
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3. INTRODUCTION
Definition :
A pharmaceutical nanosuspension is defined as “very finely
dispersed solid drug particles in an aqueous vehicle, stabilized
by surfactants, for either oral and topical use or parentral
and pulmonary administration, with reduced particle size, leading
to an increased dissolution rate and therefore improved
bioavailability”.
 Average particle size ranges from 200-600nm.
 In nanosuspension technology, the drug is maintained
in the required crystalline state with reduced particle size,
leading to an increased dissolution rate and therefore
Improved bioavailability..
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4. Need of Nanosuspension
More than 40% of drugs are poorly soluble in water, so they show problems in
formulating them in conventional dosage forms. Also, for class II which poses a
significant challenge for the formulators.
Major issues associated with poorly water-soluble compounds
Poor bioavailability.
Fed/fasted variation in bioavailability .
Lack of dose-response proportionality .
Suboptimal dosing .
Use of harsh excipients, i.e., excessive use of co-solvents and other excipients .
Use of extreme basic or acidic conditions to enhance solubilization
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5. Major Advantages of Nanosuspensions
 Can be applied for the poorly water soluble drugs.
 Reduced tissue irritation in case of subcutaneous/intramuscular
administration.
 Rapid dissolution and tissue targeting can be achieved by IV route of
administration.
 Oral
administration of nanosuspensions provide rapid and improved
bioavailability.
 Higher bioavailability and more consistent dosing in case of ocular
administration and inhalation delivery .
 Long-term physical stability due to the presence of stabilizers.
 Nanosuspensions can be incorporated in tablets, pellets, hydrogels and
suppositories
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6. Disadvantages :
Physical stability, sedimentation and compaction can causes problems.
It is bulky sufficient care must be taken during handling and transport.
Uniform and accurate dose cannot be achieved unless suspension .
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7. FORMULATION CONSIDERATIONS
 Stabilizer:lecithine,PVPK30,PVA,SLS,Cellulosics,Poloxamers,Polysorbates,
Lecithin
and
Povidones.
 Organic solvents:water miscible solvents:- ethanol & isopropanol
Partially water miscible
:- ethyl acetate, ethyl formate,butyl
lactate,
triacetin, propylene carbonate & benzyl alcohol
 Surfactants:Example: Tweens and Spans - widely used surfactants
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8. Cont……
 Co-surfactants:Transcutol, glycofurol, ethanol ,iso-propanol , bile salts Dipotassium
glycerrhizinate etc.
 Other additives:Buffers (acetate, phosphate)
cryprotectants (sucrose as sugar)
osmogent (mannitol, sorbitol).
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9. Properties of Nanosuspensions
Physical Long-term stability
Internal structure of Nanosuspensions
Adhesiveness
Crystalline state and morphology
 Increase in Saturation Solubility and Dissolution Velocity of drug
Nanosuspension Provide passive targeting
Nanosuspension provide Versatility
Nanosuspension enhance Bioavailability
Nanosuspension provide Long-term physical stability
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10. METHOD OF PREPRATION
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11. Method of preparation
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12. Microemulsions
as Templates
Bottom up
Technology
Techniques to
prepare
Nanosuspensions
Emulsions as
Templates
Hydrosols
Top down
Technology
Media Milling
Nanocrystals
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High pressure
homogenization
in water
DissoCubes
High pressure
homogenization in
non aqueous
solvents
Nanopure
Combined
precipitation and
HPH
Nanoedge
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13. Bottom up Technology: (Hydrosols)
the drug + organic solvent
Mixed with
miscible antisolvent
water-solvent mixture the drug
precipitates
Limitation
the drug needs to be
soluble in at least one
solvent and this solvent
needs to be miscible
with nonsolvent.
Top Down Technology
Media Milling (Nanocrystals),
 High Pressure Homogenization in water (Disso cubes),
 High Pressure Homogenization in non aqueous media (Nanopure)
combination of Precipitation and High-Pressure Homogenization (Nanoedege) .
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14. Media milling (NanoCrystals)
Principle
The high energy and shear forces
generated the impaction of the
milling media with the drug provide the
energy input to break the
microparticulate drug into nano-sized
particles. The milling medium is
composed of glass, zirconium oxide or
highly cross-linked polystyrene resin.
mean diameters<200nm is 30–60 min.
Advantages:
Drugs that are poorly soluble in
both aqueous and organic media
little batch-to-batch variation.
Narrow size distribution of the final
nano-sized product.
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Liversidge et al. (1992).
Fig, Schematic representation of the
media milling process
Limitations :
The major concern is the generation of
residues of milling media, which may be
introduced in the final product as
a result of erosion.
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15. High pressure homogenization
R.H.Muller developed Dissocubes technology in 1999
Operated at pressure varying from 1000-1500 bars (2800–21300psi) and up
to 2000 bars with volume capacity of 40ml (for laboratory scale).
Principle :
Based on cavitation in the aqueous phase.
The particles cavitations forces are sufficiently
high to convert the drug micro particles into
nano particles. The concern with this method
is the need for small sample particles before
loading and the fact that many cycles of
homogenization are required
Advantages
Figure:- the high-pressure
homogenization process
Disadvantages :
 Prerequisite of micronized drug
Narrow Size Distribution Of The
particles.
Nanoparticulate Drug Present In The Final Product  Prerequisite of suspension formation
Allows Aseptic Production Of Nanosuspensions using high-speed mixers before
subjecting
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For Parenteral Administration
Low Risk Of Product Contamination

16. Homogenization in non-aqueous media
Nanopure
the drug suspensions in the non- aqueous media were homogenized at 0º C
or even below the freezing point and hence are called "deep-freeze"
homogenization
Advantages :
The dispersion medium need not be removed.
Evaporation is faster and under milder conditions.
This is useful for temperature sensitive drugs.
For i.v. injections, isotonic nanosuspensions are obtained by homogenizing
in water-glycerol mixtures.
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17. Combined precipitation and homogenization
(Nanoedge)
The drug is dissolved in an organic solvent and this solution is mixed with a
miscible anti-solvent for precipitation. In the water-solvent mixture, the solubility is
low and the drug precipitates. Precipitation has also been coupled with high
shear processing.
Advantages
The major drawback of the precipitation technique, such as crystal growth
and long-term stability, can be resolved using the Nanoedge technology
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18. Nanojet technology
Principle :
Emulsions as templates Apart from the
use of emulsions as a drug delivery
vehicle,they can also be used as
templates to produce
nanosuspensions .The emulsions
templates is applicable for those
drugs that are soluble in either
volatile organic solvent or partially
water-miscible solvent.
An organic solvent or mixture of solvents
loaded with the drug is dispersed in the
aqueous
phase
containing
suitable
surfactants to form an emulsion The
organic phase is then evaporated under
reduced pressure so that
The
drug
particles
precipitate
instantaneously to form a nanosuspension
stabilized by surfactants..
Advantages :
Use of specialized equipment is not
necessary.
 Particle size can easily be controlled by
controlling
the size of the emulsion droplet.
 Ease of scale-up if formulation is
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optimized properly.

•Disadvantages
Safety concerns because of the use
of hazardous solvents in the process.
High
amount
of
surfactant/stabilizer is required as
compared
to
the
production
techniques described earlier.
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19. Microemulsions as templates
(Eccleston 1992)..
Principle :
The drug can be either loaded in the internal phase or pre-formed
microemulsions can be saturated with the drug by intimate mixing.The
suitable dilution of the microemulsion yields the drug nanosuspension
by the mechanism described earlier.
Advantages :High
Drug
Solubilization,
Long
Shelf-life
And
Ease
Of
Manufacture, Make Them An Ideal Drug Delivery Vehicle.
Need For Less Energy Input For The Production Of Nanosuspensions By
Virtue Of Microemulsions.
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20. EVALUATION PARAMETER
Evaluations of
Nanosuspensions
In Vitro Evaluation
In Vivo Evaluation
 Particle size & distribution
 Particle charge (zeta Potential)
 Crystalline state & Morphology
Saturation solubility & dissolution rate
 Solubility
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Evaluation of
surface
modified
Surface hydrophilicity
 Adhesion properties
 Interaction with body
proteins
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21. In vitro Evaluations
 Mean particle size and size distribution:
The mean particle size and the width of particle size distribution called
Polydidpersity Index are determined by Photon Correlation Spectroscopy (PCS).
Laser Diffractometry (LD) particles ranging from 0.05- 80μm upto 2000µm.
Atomic Force microscop is used for visualization of particle shape.
Particle charge (Zeta Potential):
Particle charge determines the stability of nanosuspension. For
electrostatically stabilized nanosuspension a minimum zeta potential of ±30mV
 Crystalline state and particle morphology:
Differential Scanning colorimeter (DSC) determines the crystalline
structure.. The X-Ray Diffraction[30] (XRD) is also used for determining change
in physical state and extent of amorphous drug. Scanning electron microscopy
is also used to get exact information about particle morphology.
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22. Saturation solubility and dissolution velocity:
Saturation solubility is compound specific constant depending upon
temperature and the properties of dissolution medium. Kelvin equation and
the Ostwald-Freundlich equations can explain increase in saturation
solubility
 Stability :
stabilizers are used to decrease the chances of Ostwald ripening and to
improve the stability of the suspension by providing a steric or ionic barrier.
Stabilizers like cellulosic, Poloxamers, Polysorbates, lecithin, polyoleate and
Povidones are generally used in the nanosuspensions.
PH:
Drug content:
Total volum of nanosuspension = total volum of nanosuspension x amount of drug in
aliquot/volum of aliquot
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23.  In Vivo Evaluation
Generally the formulations are administered by required route and the plasma
drug concentrations are determined by HPLC-UV visible spectrophotometry. Surface
hydrophilicity/hydrophobicity (which determines interaction with cells prior to
phagocytosis), adhesion properties and the interaction with body proteins are
generally evaluated by in vivo parameters
Interaction with body proteins :
In vitro interaction between nanoparticles and mucin can be studied by
incubation of mucin and nanoparticles (1:4 weight ratio) either in acidic or in neutral
medium. The incubation is carried out under stirring at temperature of 37ºC. The
dispersions is then be centrifuged, is incubated for 2 h at 37º C. According to
this procedure, the absorbance of mucin can be measured by colorimetry at λmax
of the drug.
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24. CURRENT MARKETED FORMULATION
Sr. no.
Product
Drug Compound
Company
1
RAPAMUNE
Sirolimus
Wyeth
2
EMEND®
Aprepitant
Merck
3
TriCor®
Fenofibrate
Abbott
4
MEGACE®ES
Megestrol Acetate
PAR Pharmaceutical
5
Avinza®
Morphine Sulphate
King Pharmaceutical
6
Focalin®XR
Dexmethylphenidate
Novartis
Hydrochloride
7
Ritalin®
Methylphenidate
Novartis
Hydrochloride
8
LA.Zanaflex
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Tizanidine
CapsulesTM
Hydrochloride
Acorda
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25. 12/13/2013
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26. PHARMACEUTICAL APPLICATIONS
 Oral Drug Delivery
 Parental Administration
 Ophthalmic Drug Delivery
 Pulmonary drug Delivery
 Target Drug Delivery
 Topical Formulations
 Mucoadhesion Of The Nanoparticles
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27. CONCLUSION
Nanosuspensions appear to be a unique and yet commercially viable
approach to poor bioavailability that are associated with the delivery of
hydrophobic drugs, including those that are poorly soluble in aqueous as well
as organic media. Production techniques such as media milling and high pressure
homogenization have been successfully for large-scale production of
nanosuspensions. Attractive features, such as increased dissolution
velocity, increased saturation solubility, improved bioadhesivity, versatility in
surface modification and ease of post-production processing, have widened the
applications of nanosuspensions for various routes.
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28. Geeta V. Yadav* And Sushma R. Singh A Review Article On Nanosuspension: A
Promising Drug Delivery System Pharmacophore (An International Research
Journal)Pharmacophore 2012, Vol. 3 (5), 217-243
Nakarani M., Misra K., Patel K.,Vaghani S., Itraconazole Nanosuspension For
Oral Delivery: Formulation, Characterization And In Vitro Comparison With
Marketed Formulation Daru Vol. 18, No. 2 2010 84-91.
Singh K.*, Chandra D., & Et.Al. Nanosuspension: Way To Enhance The
Bioavailibility Of Poorly Soluble, International Journal Of Current Trends In
Pharmaceutical Research Ijctpr, 2013: Vol. 1(4): 277-287
Shah M. , Dr. Patel N., Dr. M.R. Patel, Dr. K.R. Patel Nano Suspension: A Novel
Approch For Drug Delivery System Journal Of Pharmaceutical Science And
Bioscintific Research Volume 1,Issue 1: July-August 2011 (1-10)
. Patravale V. B., Date A. And Kulkarni R. M. A Review Article On
Nanosuspensions: A Promising Drug Delivery Strategy Journal Of Pharmaceutics
And Pharmacology Jpp 2004, 56: 827–840
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29. Patravale V. B., Date A. And Kulkarni R. M. A Review Article On Nanosuspensions: A
Promising Drug Delivery Strategy Journal Of Pharmaceutics And Pharmacology Jpp
2004, 56: 827–840
Jawahar*
N., Subramanya Nainar Meyyanathan2, Venkatachalam Senthil1,
Kuppusamy Gowthamarajan1,Kannan Elango3 Study On Studies On Physico-Chemical
And Pharmacokinetic Properties Of Olanzapine Through Nanosuspension Vol
5(10)2013; 196-202.
Chingunpituk J., A Review On Nanosuspension Technology For Drug Delivery
Walailak J Sci & Tech 2007; 4(2): 139-153.
Barrett E. Rabinow A Review On Characterization Of Drug Nanosuspensions
Workshop On Characterization Of Nanomaterials For Medical And Health Applications
May 19, 2005.
Ana Maria Mendes Cerdeira State That Production And Stabilization Of
NanosuspensionsOf Poorly Soluble Drug Substances 2007 ; 1-182
Debjit Bhowmik , G.Harish1, S.Duraivel , B. Pragathi Kumar , Vinod Raghuvanshi
Nanosuspension -A Novel Approaches In Drug Delivery System Vol. 1 No. 12 2012
50-64.
Ch.Prabhakar K.Bala Krishna A Review On Nanosuspensions In Drug Delivery
International Journal Of Pharma And Bio Sciences Voi. 2 Jan-March 2011 ;549-560.
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