3. INTRODUCTION:
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salts, excess of surfactants or stabilizing agents and
large polymer aggregates. Although, it seems obvious
to obtain highly purified nanoparticle suspensions to be
used as pharmaceutics, the purification is also needed
to obtain nanoparticle suspensions which can be
administered in vivo by a specific route.
For clinical uses, parenteral drug delivery systems
have to meet the pharmacopeia requirements of
sterility. Sterilization techniques include autoclaving,
gamma irradiation, membrane filtration, high
hydrostatic pressure sterilization.
4. TYPES:
1. Purification of Nanosuspension:
needed to remove impurities and excess of
reagents involved during manufacturing.
Depending on- i) Method of Preparation,
ii) Org. Solvent,
iii) Oil,
iv) Surfactants,
v) Polymerization initiators.
Methods:
I. Evaporation under reduced pressure,
II. Centrifugation Tech.
III. Ultra-Centrifugation Tech.
IV. Filtration Through Mesh/filter
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5. I. Evaporation under reduced pressure: to remove
large quantities of volatile organic solvents and a
part of water.
II. Centrifugation Tech.: to remove aggregates and
large particles.
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6. III. Ultra-Centrifugation Tech.: performed at 100,000–
110,000 rpm for 30 to 45 min.
III. Filtration Through Mesh/filter: to remove large particles
or polymer aggregates which formed during
preparations .
2. Sterilization:
- Req. for parenteral drug delivery system.
Method:
I. Heat sterilization / moist sterilization / autoclaving,
II. Gamma Irradiation,
III. Membrane filtration,
IV. High Hydrostatic Pressure (HPP). 6
7. I. Heat sterilization / moist sterilization / autoclaving,:
-high temperatures (120°C).
II. Gamma Irradiation:
Adv: -to insure a homogeneous sterilization.
Disadv.:
PCL nanoparticles resulted in an increase of
molecular weight due to cross-linking reactions
occurring between polymer chains or between
PCL and surfactants .
induce fragmentation of covalent bonds & produces
free radicals.
III. Membrane filtration:
alternative method for chemically or thermally
sensitive material .
applied for only a low viscosity containing NP’s.
not suitable for larger or in the range of 220 nm.
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8. IV. High Hydrostatic Pressure (HPP):
Adv.:
Didn’t induce physical damage on the different
nanoparticle suspensions.
Didn’t modify physically or chemically the
poly(alkylcyanoacrylate) nanospheres.
to destroy all vegetative microorganisms.
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9. 3. Drying of NP’s:
storage of nanoparticles as suspensions presents
many disadvantages such as :
I. Microbiological Contamination,
II. Premature Polymer degradation by hydrolysis
III. Physicochemical instability due to:
- particle aggregation,
- sedimentation,
- loss of the biological activity of the drug.
Method:
A. Freeze Drying of Nanoparticles ,
B. Spray-drying.
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10. A. Freeze Drying of Nanoparticles :
- lyophilization,
Principle: removing water content of a frozen
sample by sublimation and desorption under
vacuum.
Steps:
a) freezing of the sample (solidification),
b) 1ºdrying corresponding to the ice sublimation
c) 2ºdrying corresponding to desorption of
unfrozen water.
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11. B. Spray-drying:
-transforms liquids into dried particles under a
continuous process,
-alternative to freeze-drying,
Advantages:
a) low price,
b) rapid process,
c) possibility to modulate physicochemical
characteristics of the produced powders by
varying process parameters.
Steps:
(1) atomization of the feed, i.e. nanoparticle
suspension into a spray,
(2) spray-air contact,
(3) drying of the spray ,
(4) separation of the dried product from the drying
gas.
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12. REFERENCES:
1) C. A. Nguyen, E. Allemann, G. Schwach, E. Doelker, and
R. Gurny. Synthesis of a novel fluorescent poly (DL,-
lactide) endcapped with 1-pyrenebutanol used for the
preparation of nanoparticles. Eur. J. Pharm. Sci. 20:217–
222 (2003).
2) P. Beck, D. Scherer, and J. Kreuter. Separation of drug-
loaded nanoparticles from free drug by gel filtration. J.
Microencapsul. 7:491– 496 (1990).
3) G. Tishchenko, K. Luetzow, J. Schauer, W. Albrecht, and
M. Bleha. Purification of polymer nanoparticles by
diafiltration with polysulfone/hydrophilic polymer blend
membranes. Sep. Purif. Technol. 22–23:403–415 (2001).
4) G. Tishchenko, R. Hilke, W. Albrecht, J. Schauer, K.
Luetzow, Z. Pientka, and M. Bleha. Ultrafiltration and
microfiltration membranes in latex purification by
diafiltration with suction. Sep. Purif. Technol. 30:57–68
(2003).
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13. 5. E. Allémann, E. Doelker, and R. Gurny. Drug loaded poly
(lactic acid) nanoparticles produced by a reversible salting-
out process: purification of an injectable dosage form. Eur.
J. Pharm. Biopharm. 39:13–18 (1993).
6. J. Rollot, P. Couvreur, L. Roblot-Treupel, and F. Puisieux.
Physicochemical and morphological characterization of
polyisobutylcyanoacrylate nanocapsules. J. Pharm. Sci.
75:361–364 (1986).
7. V. Masson, F. Maurin, H. Fessi, and J. P. Devissaguet.
Influence of sterilization processes on poly(ε-caprolactone)
nanospheres. Biomaterials. 18:327–335 (1997).
8. P. Sommerfeld, U. Schroeder, and B. A. Sabel.
Sterilization of unloaded polybutylcyanoacrylate
nanoparticles. Int. J. Pharm. 164:113– 118 (1998).
9. E. Memisoglu-Bilensoy, and A. A. Hincal. Sterile, injectable
cyclodextrin nanoparticles: Effects of gamma irradiation
and autoclaving. Int. J. Pharm. 311:203–208 (2006).
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14. 10) W. Abdelwahed, G. Degobert, and H. Fessi. Freeze-drying
of nanocapsules: Impact of annealing on the drying
process. Int. J. Pharm. 324:74–82 (2006).
11) F. De Jaeghere, E. Allémann, J. -C. Leroux, W. Stevels, J.
Feijen, E. Doelker, and R. Gurny. Formulation and
lyoprotection of poly (Lactic acidco-ethylene oxide)
nanoparticles: influence on physical stability and in vitro cell
uptake. Pharm. Res. 16:859–866 (1999).
12) M. Sameti, G. Bohr, M. N. V. Ravi Kumar, C. Kneuer, U.
Bakowsky, M. Nacken, H. Schmidt, and C. -M. Lehr.
Stabilization by freeze-drying of cationically modified silica
nanoparticles for gene delivery. Int. J. Pharm. 266:51–60
(2003).
13) C. R. Müller, V. L. Bassani, A. R. Pohlmann, C. B.
Michalowski, P. R. Petrovick, and S. S. Guterres.
Preparation and characterization of spraydried
nanocapsules. Drug. Dev. Ind. Pharm. 26:343–347 (2000).
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