Seminar on nanosuspension
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Transcript of Seminar on nanosuspension
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A SEMINAR ON
NANOSUSPENSIONPresented 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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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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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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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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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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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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METHODS OF PREPARATION 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
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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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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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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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.
5) HIGH PRESSURE HOMOGENIZATION
AdvantagesLow 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
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HIGH PRESSURE HOMOGENIZATION
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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)
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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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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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.
Advantage: Drawback of the precipitation technique, such as crystal growth and long-term stability, can be resolved
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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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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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SOLVENT EVAPORATION METHOD
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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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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)
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 DrugEntrapment 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
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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:
CHARACTERIZATION OF NANOSUSPENSION
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CURRENT MARKETED FORMULATION
Sr. no. Product Drug Compound Company1 RAPAMUNE Sirolimus Wyeth2 EMEND® Aprepitant Merck3 TriCor® Fenofibrate Abbott4 MEGACE®ES Megestrol Acetate PAR
Pharmaceutical5 Avinza® Morphine
SulphateKing Pharmaceutical
6 Focalin®XR Dexmethylphenidate Hydrochloride
Novartis
PHARMACEUTICAL APPLICATIONS
Oral Drug Delivery
Parental Administration
Ophthalmic Drug Delivery
Pulmonary drug Delivery
Target Drug Delivery
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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.
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, 98-106Mudgil, 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
THANK YOU
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