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RECOVERY OF
NANOPARTICLES.
Presented by:
TALPE SHUBHAM MARUTI
M.Pharm sem-III
(Pharmaceutics)
Under the Guidance of:
MR.SAYYAD S.F.
AMRUTVAHINI SHETI AND SHIKSHAN VIKAS SANSTHA’S
AMRUTVAHINI COLLEGE OF PHARMACY,
SANGAMNER 422 608
CONTENTS:
 INTRODUCTION
 TYPES:
1) Purification of nanosuspension,
2) Sterilization,
3) Drying of nanoparticles,
 CONCLUSIN
 REFERENCES.
12/19/2017
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INTRODUCTION:
12/19/2017
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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.
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
12/19/2017
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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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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
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.
12/19/2017
7
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.
8
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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9
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.
12/19/2017
10
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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11
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).
12/19/2017
12
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).
13
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).
14
12/19/2017
15

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Recovery and Processing of Nanoparticles

  • 1. RECOVERY OF NANOPARTICLES. Presented by: TALPE SHUBHAM MARUTI M.Pharm sem-III (Pharmaceutics) Under the Guidance of: MR.SAYYAD S.F. AMRUTVAHINI SHETI AND SHIKSHAN VIKAS SANSTHA’S AMRUTVAHINI COLLEGE OF PHARMACY, SANGAMNER 422 608
  • 2. CONTENTS:  INTRODUCTION  TYPES: 1) Purification of nanosuspension, 2) Sterilization, 3) Drying of nanoparticles,  CONCLUSIN  REFERENCES. 12/19/2017 2
  • 3. INTRODUCTION: 12/19/2017 3  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 12/19/2017 4
  • 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. 12/19/2017 5
  • 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. 12/19/2017 7
  • 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. 8
  • 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. 12/19/2017 9
  • 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. 12/19/2017 10
  • 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. 12/19/2017 11
  • 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). 12/19/2017 12
  • 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). 13
  • 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). 14