A Review on Nanosuspension

1. A SEMINAR ON
NANOSUSPENSION
Presented by,
OMKAR S. BHANDWALKAR
M. Pharm. Sem.-I,
Under the guidance of,
Asso. Prof. Dr. P. K. PAWAR
Head of Department,
Dept. of Pharmaceutics
Gourishankar Institute of Pharmaceutical Education and
Research, Limb, Satara.
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2. CONTENTS
 Introduction
 Need of Nanosuspension
 Advantages of Nanosuspension
 Disadvantages of Nanosuspension
 Method Of Preparation
 Formulation Considerations
 Characterization of Nanosuspension
 Current Marketed Formulations
 Pharmaceutical Applications
 Conclusion
 References
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3. INTRODUCTION
 Definition:
“A very finely dispersed solid drug particles in an aqueous
vehicle in which diameter of suspended particle is less than 1 µm in
size, 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 200-600 nm.
 In nanosuspension technology, the drug is maintained in the
required crystalline state with reduced particle size, Improved
bioavailability leading to an increased dissolution rate.
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4. NEED OF NANOSUSPENSION
 Poor bioavailability.
 Lack of dose-response proportionality .
 Use of harsh excipients, i.e., excessive use of co-
solvents and other excipients .
 Use of extreme basic or acidic conditions to
enhance solubilization
 Use for poorly water soluble as well as poorly organic
soluble drugs
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5. ADVANTAGES
 Can be applied for the poorly water soluble
drugs.
 Rapid dissolution and tissue targeting can be
achieved by IV route of administration.
 Oral administration of nanosuspensions provide
rapid and improved bioavailability.
 Long-term physical stability due to the
presence of stabilizers.
 Nanosuspensions can be incorporated in
tablets, pellets, hydrogels.
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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. METHODS OF PREPARATION
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1) PRECIPITATION METHOD
2) MICROEMULSION TEMPLATE
3) MEDIA MILLING
4) HIGH PRESSURE HOMOGENIZATION
5) HOMOGENIZATION IN AQ. MEDIA
6) HOMOGENIZATION IN NON AQ.
MEDIA
7) NANOJET TECHNOLOGY
8) NANOEDGE
9) SUPERCRITICAL FLUID METHOD
10) SOLVENT EVAPORATION METHOD
11) CO-GRINDING METHOD

8. 1. PRECIPITATION METHOD
drug + organic solvent
mixed with
miscible antisolvent
precipitation
Advantages:
•Simple Process
•Low cost of Equipments
Disadvantages:
•Drug needs to be soluble in at least one solvent and
this solvent needs to be miscible with nonsolvent
•Crystal Growth
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9. 2) MICROEMULSIONS TEMPLATE:
Dispersion of two immiscible liquids
Stabilized by Surfactant or Cosurfactant
Advantages :-
High Drug Solubilization, Long Shelf-life And Ease Of Manufacture
 Uniform particle distribution
Disadvantages:
Requires high amount of Surfactants and Stabilizers
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10. 3) MELT EMULSIFICATION METHOD
Drug + Aq. Solution having stabilizer
Heated this solution above Melting Point of Drug
Homogenized by High Pressure Homogenizer for formation
of Emulsion
Emulsion is cooled to Precipitate
Advantages :-
Avoidance of organic solvent
Disadvantages:
Formation of large particles
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11. 4) MEDIA MILLING:
Advantages:
Drugs that are poorly soluble in both aqueous and organic
media
Disadvantages:
Nanosuspension contaminated with materials eroded from balls
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The Nanosuspension is prepared by high share media mills. The
milling Chamber charged with Milling media, Water, Drug, Stabilizer
is rotated at very high shear rate at controlled temperature.
The milling medium is composed of Glass, Zirconium oxide and
highly cross linked polystyrene resin.

12. 5) HIGH PRESSURE HOMOGENIZATION
Advantages
Low Risk Of Product Contamination
Allows Aseptic Production of Nanosuspensions For Parenteral
Administration
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Drug + Stabilizer to form Presuspension
Presuspension is homogenized by High Pressure homogenizer at low
pressure
Homogenized at high pressure

13. 13
HIGH PRESSURE HOMOGENIZATION

14. 6) HOMOGENIZATION IN AQUEOUS MEDIA
 Forcing the of the suspension under pressure
through a narrow aperature valve.
 Dissocubes was developed by Muller et al in 1999.
 This instrument can be operated at pressure
varying from 100-1500 bars (2800-21300 psi)
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15. 7) HOMOGENIZATION IN NON-AQUEOUS MEDIA
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 :
Evaporation is faster and under milder conditions.
This is useful for temperature sensitive drugs.
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16. 8) NANOJET TECHNOLOGY
 This technique uses a chamber where stream of
suspension divided into more parts which colloid with
each other at high pressure.
 The high shear force produced during process results in
particle size reduction.
 Disadvantage: obtained product contains larger particles
of microemulsion.
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17. 9) NANOEDGE
 It is a combined method of Precipitation and
Homogenization.
 The drug is dissolved in an organic solvent
and this solution is mixed with a miscible anti-
solvent for precipitation.
 The precipitated particle suspension is
homogenized.
17Advantage: Drawback of the precipitation technique, such as crystal
growth and long-term stability, can be resolved

18. 10) SUPERCRITICAL FLUID METHOD
 In this process micronization of drug particles within
narrow range of particle size is carrird out.
 It forms particles size range 5-2000 nm in diameter.
 Disadvantage:
Surfactants in Supercritical CO2 and high pressure
requires
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19. 11) SOLVENT EVAPORATION METHOD
Drug + Polymer in organic solvent
Dropped by syringe in dist. water containing
surfactant
Homogenized using magnetic stirrer
Solvent removal by air drying
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20. 20
SOLVENT EVAPORATION METHOD

21. CO-GRINDING METHOD
 Nanosuspension is also prepared by dry milling
techniques.
 In this method, dry grinding of poorly water soluble
drugs with soluble polymers and copolymers are
dispersing in liquid medium.
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22. FORMULATION CONSIDERATIONS
 Stabilizer:-
Lecithine, PVPK 30, PVA, SLS, Poloxamers, Polysorbates,
 Organic solvents:-
water miscible solvents:- ethanol & isopropanol
Partially water miscible :- ethyl acetate, ethyl formate,butyl lactate, triacetin,
propylene carbonate & benzyl alcohol
 Surfactants:-
Tweens and Spans - widely used surfactants
 Co-surfactants:-
Transcutol, glycofurol, ethanol ,iso-propanol , bile salts Dipotassium
glycerrhizinate etc.
 Other additives:-
Buffers (acetate, phosphate)
cryprotectants (sucrose as sugar) 22

23. In vitro Evaluations:
 Mean particle size and size distribution:
•The mean particle size distribution and its ranges named Polydispersity index (PI)
is measured by Laser Diffractometry (LD), Photon Correlation Spectroscopy and
Coulter Counter method. PI gives the physical stability. A PI value 0.1 – 0.25 shows
narrow size distribution.
•LD can detect and quantify drug microparticles and also gives volume size distribution.
•The Coulter counter gives the absolute no. of particles per volume for the different size
classes.
Drug Entrapment Efficiency:
Initial Drug – Free Drug
Entrapment Efficiency (%) = × 100
Initial Drug
 Transmission Electron Microscopy (TEM):
For the morphological evaluation of nanoparticles.
Fourier Transform Infrared Spectroscopy (FTIR):
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CHARACTERIZATION OF NANOSUSPENSION

24.  X-ray Powder Diffraction (XPRD):
 Differential Scanning Calorimetry (DSC):
 Particle charge (Zeta Potential):
Particle charge determines the stability of
nanosuspension.
For electrostatically stabilized nanosuspension a
minimum zeta potential of ±30 mV
 In Vitro Drug Release:
 Saturation Solubility:
 Stability Study:
 In Vivo Evaluation:
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CHARACTERIZATION OF NANOSUSPENSION

25. 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
Hydrochloride
Novartis
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26. PHARMACEUTICAL APPLICATIONS
 Oral Drug Delivery
 Parental Administration
 Ophthalmic Drug Delivery
 Pulmonary drug Delivery
 Target Drug Delivery
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27. CONCLUSION
Nanosuspension solved the poor bioavailability problems of poorly water as well
as organic soluble drugs. Media milling and High Pressure Homogenizer are used for
large scale production of Nanosuspension. Nanosuspension can be administered
through Oral, Parenteral, Pulmonary and Ocular routes. Nanosuspension is simple,
less requirements of excipients, increased dissolution rate and saturation solubility.
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28. Patel, V., Agrawal, Y., 2011. Nanosuspension: An Approach to Enhance
Solubility of Drugs. Journal of Advance Pharmaceutical Technology, 81-87.
Shid, R., Dhole, S., Kulkarni, N., Shid, S.,2013. Nanosuspension: A
Review. International Journal of Pharmaceutical Sciences Review and
Research, 98-106
Mudgil, M., Pawar, P., 2013. Preparation and In Vitro/Ex Vivo Evaluation
of Moxifloxacin-Loaded PLGA Nanosuspension for Opthalmic Application.
Scientia Pharmaceutica, 591-606.
Kamble, V., Jagdale, D., Kadam, V., 2010. Nanosuspension A Novel
Drug Delivery system. International Journal of Pharma and Bio Sciences,
352-360.
Wagh, K., Patil, S., Akarte, A., Baviskar, D., Nanosuspension- A New
Approach of Bioavailability Enhancement. International Journal of
Pharmaceutical Sciences Review and Research, 61-65.
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REFERENCES

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