This document provides an overview of nanosuspensions. It defines nanosuspensions as colloidal dispersions of nanosized drug particles stabilized by surfactants with particle sizes less than 1 micrometer. The key benefits of nanosuspensions are improved dissolution velocity, saturation solubility, and bioavailability for poorly soluble drugs. Common preparation methods include wet milling, high pressure homogenization, and precipitation with a compressed antisolvent. Characterization techniques involve measuring particle size, zeta potential, crystal morphology, and dissolution. Nanosuspensions can enhance bioavailability and enable targeted and controlled drug delivery through various administration routes.

1. NANOSUSPENSION
Presented by:
Sufyanu Sulaiman
M.Pharm (Pharmaceutics) 2nd
Semester
Jamia Hamdard
University

2. CONTENTS:
1.INTRODUCTION
2.WHY NANOSUSPENSION
3. TYPES
4. METHOD OF PREPARATION
5.PROPERTIES
6. CHARACTARIZATION
7.APPLICATION
8.CONCLUSION
9.REFERENCE

3. INTRODUCTION:
DEFINITIONS:
Nanosuspension are “colloidal dispersion of nanosized drug particle
stabilized by surfactant”.particle size of nanosuspension is less than 1
micrometer or 200-600 nm
First nanosuspension product in market was RAPAMUNE
,introduced in 2000 by company WYETH
2nd
product was “EMEND”In 2001 by MERCK ,for emesis

4. WHY NANOSUSPENSION?
To improve stability & bioavailability of
poorly soluble drug ,poorly permeable drug by
increasing dissolution due to very small particle
size.
To improve dissolution velocity and saturation
solubility.
To increase bioadhesiveness.

5. • Broadly applicable: Exploits non-specific property of insolubility
• Small particle size: 300 nm to 10 microns (vol weighted mean)
• High loading:=Low volume doses 10 – 200 mg/Ml
• Elimination of cosolvents: increased safety = increased dose
• Long-term stability: up to 2 yrs at RT or 5°C
• Dosing: injection: IV, IM, ID ,oral, respiratory and other routes
• can be used for controlled and targeted delivery of drug.
FEATURES OF NANOSUSPENSION

6.  Four main categories:
(a) solid or crystalline drug nanosuspensions:
stabilized with the help of surfactants or polymers.
b) polymeric-coated drug nanosuspensions or
polymeric nanoparticles: the drug is coated or
encapsulated within a polymer matrix or capsule,
such
as poly (lactic-co-glycolic acid) (PLGA), poly (butyl
cyanoacrylate) (PBCA), etc.
(c) solid lipid nanoparticles, where the drug is
entrapped in a lipid matrix

7. (d) liposomes, which are spherical
phospholipid bilayer vesicles containing the
drug dissolved or dispersed in either
the inner aqueous compartment or the lipid
bilayer.

8. METHOD OF PREPARATION:
There are various method of preparation:
• Top down processes:
1.micronization by colloid or jet milling
2. High Pressure Homogenization
3. Microfluidization
• Bottom up processes:
1, Solvent Anti-solvent
2. Supercritical Fluid Process
a) Supercritical fluid as a solvent (RESS /
RESOLV).
b) Supercritical fluid as an antisolvent
(GAS/SAS/ASES/SEDS).
c) Emulsion-Solvent Evaporation.
d) Spray Drying.
• Combination processes.

9. WET MILLING
By using high shear media mills /pearl mills made of ceramic
sintered aluminium oxide or zirconium oxide or highly
crosslinked polystyrene resin.
Principle:combined force of impact & friction
Example:planetry mills (<0.1µm) ,for preparation of insulin
zinc nanosuspension

10. Elan Lab Scale NanoMillTM for batch production of nanosuspensions. Milling media, drug,
stabilizer, and optional surfactant in an aqueous medium are added to the water-jacketed
milling chamber. The chamber is attached to the rotating shaft with a clamp. The gap between
the shaft
and milling chamber inner surface is small such that high shear is generated when the shaft
rotates. The shaft can rotate up to 6000 rpm, forcing drug to impinge against itself,
the milling media, and the milling chamber, resulting in
attrition.

11. Basic homogenization principles: piston-gap (left) and jet-stream
arrangement (right).
•In the piston-gap homogenizer the macrosuspension coming from the
sample container is forced to pass through a tiny gap (e.g., 10
mm),particle diminution is affected by shear force, cavitation, and
impaction.
•In jet-stream homogenizers the collision of two high-velocity
streams leads to particle diminution mainly by impact forces.

12. PC: product container
H: homogenization block
T: double walled tube
Ref: Wolfgang Mehnert et. al.; SLN Production, Characterization & Applications; Adv. Drug Del.
Rev.; 47 (2001) 165-196.

13. 
Piston-gap homogenization in water
(Dissocubes)
.
The suspension is pressed through a very narrow ring gap. The
gap width is typically in the range of 3-15 micrometer atm
pressures
between 1500-150 bar. There is a high streaming velocity.

14. HOMOGENISATION:
It can be done by four methods:
a) Dissocubes
b)nanopure technology/deep freeze homogenisation
c)nano edge method
d)nanojet/opposite stream

15.  Nanocrystals should be incorporated in traditional dry
dosage form, e.g. tablets, pellets and capsules. An elegant
method to obtain a final formulation directly is the production
of nanocrystals in non-aqueous homogenization media.
 Drug nanocrystals dispersed in liquid polyethylene glycol
(PEG) or oils can be directly filled as drug suspensions into
gelatine or HPMC capsules.Efficient particle diminution could
also be obtained in non-aqueous media.
To obtain isotonic nanosuspensions for intravenous injection,
it is beneficial to homogenize in water-glycerol mixtures.

16. NANO PURE TECHNOLOGY:
Drug suspension in non aqueous media were homogenized at
0°c or even below freezing point.
 NANOEDGE METHOD:
A Combinative technology.
Principle: precipitation+homogenization.
Preciptation is performed in water miscible solvent (ethanol,
methanol)& is evaporation is done to remove solvent free media.
advantage-no crystal growth
 NANOJET/OPPOSITE STREAM:
This stream of suspension is divided into 2 or more parts ,which
collide with each other at high pressure e.g atovaquone
nanosuspension by microfluidizer

17. Schematic of RESS process
Schematic of SAS process

18. SUPERCRITICAL FLUID TECHNOLOGY:
 It produce nanoparticle from drug solution .
Method:
•RESS(RAPID EXPANSION OF SUPER CRITICAL
SOLUTION PROCESS):It involves the expansion of drug
solution in supercritical fluid through a nozzle which leads to
loss of solvent power of supercritical fluid resulting
precipitation
e.g cyclosporine nanoparticle (400-700 nm)
•PRECIPTATION WITH COMPRESSED ANTISOLVENT
PROCESS(PCA):in this drug solution is atomized into a
chamber containing compressed CO2 ,as the solution is
removed ,solution get supersaturated & thus ppt as fine
crystal.

19. .
:
Emulsification-solvent evaporation
technique
This technique involves preparing a solution of drug followed by its
emulsification in another liquid that is a non-solvent for the drug.
Evaporation of the solvent leads to precipitation of the drug.
Crystal growth and particle aggregation can be controlled by
creating high shear forces using a high-speed stirrer.
Hydrosol method
This is similar to the emulsification- solvent evaporation method.
The only difference between the two methods is that the drug
solvent is miscible with the drug anti-solvent. Higher shear force
prevents crystal growth and Ostwald ripening and ensures that the
precipitates remain smaller in size.

20. Particle size distribution:
 The particle size distribution can be determined by photon
correlation spectroscopy (PCS), laser diffraction (LD) and coulter
counter multisizer.
 The PCS method can measure particles in the size range of 3
nm to 3 μm and the LD method has a measuring range of 0.05-80
μm.
The coulter counter multisizer gives the absolute number of
particles, in contrast to the LD method, which gives only a
relative size distribution.
For IV use, particles should be less than 5 μm, considering that
the smallest size of the capillaries is 5-6 μm and hence a higher
particle size can lead to capillary blockade and embolism.

21. Zeta potential
Zeta potential is an indication of the stability of the suspension. For a
stable suspension stabilized only by electrostatic repulsion, a minimum
zeta potential of ±30 mV is required whereas in case of a combined
electrostatic and steric stabilizer, a zeta potential of ±20 mV would be
sufficient.
Crystal morphology
To characterize the polymorphic changes due to the impact of high-
pressure homogenization in the crystalline structure of the drug,
techniques like X-ray diffraction analysis in combination with
differential scanning calorimetry or differential thermal analysis can be
utilized. Nanosuspensions can undergo a change in the crystalline
structure, which may be to an amorphous form or to other polymorphic
forms because of high-pressure homogenization.

22. Dissolution:
• It can increase the dissolution velocity as well as the saturation
solubility. The assessment of saturation solubility and
dissolution velocity helps in determining the in vitro behavior of
the formulation.
Böhm et al. reported an increase in the dissolution pressure as
well as dissolution velocity with a reduction in the particle size
to the nanometer range. Size reduction leads to an increase in
the dissolution pressure. An increase in solubility that occurs
with relatively low particle size reduction may be mainly due to
a change in the surface tension leading to an increased
saturation solubility

23.  The high surface energy of nanosized particles induces
agglomeration of the drug crystals. The main function of the
stabilizer is to wet the drug particles thoroughly to prevent
Ostwald ripening and agglomeration of the nanosuspension
and form a physically stable formulation by providing a steric
or an ionic barrier.
 Typical examples of stabilizers used in nanosuspensions
are cellulosics, poloxamer, polysorbates, lecithin, polyoleate
and povidones. Lecithin may be preferred in developing
parenteral nanosuspensions.
Stability of Nanosuspensions:

24. Enhanced
bioavailability
Site-specific
targeting
Controlled
release
Ocular delivery
Oral delivery
Pulmonary delivery
Systemic delivery
Dermatological

25. Application of nanosuspension
.Bioavailability enhancement
Nanosuspensions resolve the problem of poor
bioavailability by solving the twin problems of poor solubility and
poor permeability across the membrane. Oral administration of
the gonadotrophin inhibitor Danazol as nanosuspension leads to an
absolute bioavailability of 82.3 and the conventional dispersion
(Danocrine) only to 5.2
Bioavailability of poorly soluble oleanolic acid, a
hepatoprotective agent, was improved using a nanosuspension .

26. Intravenous administration:.
• IV administration results in several advantages, such as administration
of poorly soluble drugs without using a higher concentration of toxic co-
solvents, improving the therapeutic effect of the drug available as
conventional oral formulations and targeting the drug to macrophages
and the pathogenic microorganisms residing in the macrophages.
Injectable nanosuspensions of poorly soluble drug tarazepide have
been prepared to overcome the limited success achieved using
conventional solubilization techniques, such as use of surfactants,
cyclodextrins, etc., to improve bioavailability.

27. cloricromene nanosuspension by
using eudragit
Reduced irritation
Reduced ocular toxicity
Pentration in posterior segment
Increased intravetrial t half
Sustained release
 Sustain drug release
 Minimum ocular toxicity
 Prolong intra vitreal t ½
 Less frequent dosing
 Penetration to posterior segment
 Less irritation
Target Achievement nanosuspension
Device

28. Drug targeting
Nanosuspensions can also be used for targeting as their
surface properties and changing of the stabilizer can easily
alter the in vivo behavior. The drug will be up taken by the
mononuclear phagocytic system to allow regional-specific
delivery.
This can be used for targeting anti-mycobacterial, fungal or
leishmanial drugs to the macrophages if the infectious
pathogen is persisting intracellularly.
Kayser formulated a nanosuspension of Aphidicolin to
improve drug targeting against leishmania-infected
macrophages.

29. Mucoadhesion of the nanoparticles
 The particles are immobilized at the intestinal surface by an adhesion
mechanism referred to as "bioadhesion." From this moment on, the
concentrated suspension acts as a reservoir of particles and an adsorption
process takes place very rapidly.
The adhesiveness of the nanosuspensions not only helps to improve
bioavailability but also improves targeting of the parasites persisting in
the GIT, e.g., Cryptosporidium parvum.
Bupravaquone nanosuspensions have been reported to demonstrate an
advantage in TRC- alpha-deficient mice infected with Cryptosporidium
parvum oocytes.
The bioadhesion can also be improved by including a mucoadhesive
polymer in the formulation.

30. Pulmonary administration:
Aqueous nanosuspensions can be nebulized using mechanical or
ultrasonic nebulizers for lung delivery. Because of their small size,
it is likely that in each aerosol droplet at least one drug particle is
contained, leading to a more uniform distribution of the drug in
lungs.
The pharmacokinetics of the nebulized nanocrystal budenoside
suspension showed comparable AUC, higher Cmax and lower
Tmax as that of the pulmicort respules.

31. Nanosuspensions of pure drug offer a method to formulate poorly
soluble drug and enhance the bioavailability of several drugs. It has
many formulations and therapeutic advantages, such as simple
method of preparation, less requirement of excipients, increased
dissolution velocity and saturation solubility, improved adhesion,
increases the bioavailability leading to a decrease in the dose and
fast-fed variability and ease of large-scale manufacturing.
 This technology is gaining significance as the number of
molecules with solubility and bioavailability related problems are
increasing day by day. Thus, nanotechnology can play a vital role in
drug discovery programs to increase aqueous solubility as well as
bioavailability of poorly soluble drugs.
CONCLUSION:

34. REFERENCE:
1. International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491 Vol 2, Suppl 4, 2010
NANOSUSPENSION
TECHNOLOGY: A REVIEW
PRASANNA LAKSHMI*1, GIDDAM ASHWINI KUMAR1
Bharat Institute of Technology, Mangalpally(v), Ibrahimpatnam(Md),
2. Nanosuspensions: a promising drug delivery strategy
V. B. Patravale, Abhijit A. Date and R. M. Kulkarni
Journal of pharmacy and pharmacology JPP 2004, 56: 827–840
2004 The Authors
Received December 11, 2003
Accepted March 30, 2004
DOI 10.1211/0022357023691

35. 3. Walailak J Sci & Tech 2007; 4(2): 139-153
Nanosuspension Technology For Drug Delivery
Jiraporn CHINGUNPITUK
School Of Pharmacy, Walailak University, Nakhon Si Thammarat 80161, Thailand.
4. Alok K. Kulshreshtha ● Onkar N. Singh
G. Michael Wall
Editors
Pharmaceutical Suspensions
From Formulation Development
To Manufacturing
Page; 27- 56, 276-236
5. WWW.PUBMED.COM
6 . WWW.Pharmainfo.net