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Physicochemical Parameters Associated with Nanoparticle Formation in the Salting-Out, Emulsification-Diffusion, and Nanoprecipitation Methods

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Abstract

Purpose. The aim of this work was to relate the physicochemical properties of the aqueous and organic phases used for nanoparticle (NP) preparation to the formation of NP produced by salting-out, emulsification-diffusion, and nanoprecipitation.

Methods. Methacrylic acid copolymer and poly(vinyl alcohol) (PVAL) were selected as NP polymer and emulsifying agent, respectively. Salting-out and emulsification-diffusion NP batches were prepared modifying the PVAL content in the aqueous phase. For nanoprecipitation, NP were produced with variation of the polymer content and type of solvent in the organic phase.

Results. For salting-out and emulsification-diffusion, NP formation was discussed in terms of the emulsification theory. The nanoemulsion obtained during NP preparation was visualized by scanning electron microscopy. Aqueous and organic phases used for NP preparation were characterized by their viscosity and surface tension. NP characteristics such as particle mean size, residual surfactant, suspendability in water after freeze-drying, and morphology were explained in terms of these properties. For nanoprecipitation, NP formation was analyzed considering the diffusion-stranding phenomenon.

Conclusions. NP formation by salting-out and emulsification-diffusion was related to PVAL chain interactions at the droplet interface (e.g., reduction in the interfacial tension, mechanical sta- bilization, and steric stabilization) and in the bulk solution (hy- drodynamic stabilization). For nanoprecipitation, χsolvent-water and Δδsolvent-water of the organic phase solvents were well related to the NP characteristics.

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REFERENCES

  1. S. Davis. Biomedical applications of particle engineering. In R. H. R. Coombs and W. D. Robinson (eds.), Nanotechnology in Medicine and the Biosciences, Gordon & Breach, Amsterdam, The Netherlands, 1996, pp. 243–262.

    Google Scholar 

  2. F. De Jaeghere, E. Doelker, and R. Gurny. Nanoparticles. In E. Mathiowitz (ed), Encyclopedia of Controlled Drug Delivery, John Wiley, New York, 1999, pp. 641–664.

    Google Scholar 

  3. S. M. Moghimi, A. C. Hunter, and J. C. Murray. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol. Rev. 53:283–318 (2001).

    Google Scholar 

  4. P. Couvreur, G. Barratt, E. Fattal, P. Legrand, and C. Vauthier. Nanocapsule technology: a review. Crit. Rev. Ther. Drug Carrier Syst. 19:99–134 (2002). Galindo-Rodriguez et al. 1438

    Google Scholar 

  5. K. S. Soppimath, T. M. Aminabhavi, A. R. Kulkarni, and W. E. Rudzinski. Biodegradable polymeric nanoparticles as drug delivery devices. J. Control. Rel. 70:1–20 (2001).

    Google Scholar 

  6. M. L. Hans and A. M. Lowman. Biodegradable nanoparticles for drug delivery and targeting. Curr. Opin. Solid State Mater. Sci. 6:319–327 (2002).

    Google Scholar 

  7. A. T. Florence. The oral absorption of micro-and nanoparticulates: neither exceptional nor unusual.Pharm. Res. 14:259–266 (1997).

    Google Scholar 

  8. C. Bindschaedler, R. Gurny, and E. Doelker. Process for preparing a powder of water-insoluble polymer which can be redispersed in a liquid phase, the resulting powder and utilization thereof. Priority country: Switzerland, October 20, 1988. Patent WO 88/08011 (1988).

  9. J. C. Leroux, E. Allemann, E. Doelker, and R. Gurny. New approach for the preparation of nanoparticles by an emulsificationdiffusion method. Eur. J. Pharm. Biopharm. 41:14–18 (1995).

    Google Scholar 

  10. H. Fessi, F. Puisieux, J. P. Devissaguet, N. Ammoury, and S. Benita. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int. J. Pharm. 55:R1–R4 (1989).

    Google Scholar 

  11. E. Allemann, 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).

    Google Scholar 

  12. T. Kasemura, S. Takahashi, N. Nakane, and T. Maegawa. Surface dynamics for poly(vinyl alkylate)s via dynamic contact angle and adhesion tension relaxation. Polymer 37:3659–3664 (1996).

    Google Scholar 

  13. J. M. G. Lankveld and J. Lyklema. Adsorption of polyvinyl alcohol on the paraffin-water interface. I. Interfacial tensions as a function of time and concentration. J. Colloid Interface Sci. 41: 454–465 (1972).

    Google Scholar 

  14. P. Alexandridis, V. Athanassiou, S. Fukuda, and A. T. Hatton. Surface activity of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) copolymers. Langmuir 10: 2604–2612 (1994).

    Google Scholar 

  15. F. Tadros. Stability of oil-in-water emulsions in polymersurfactant complexes. Paraffin-water emulsions in mixtures of poly(vinyl alcohol) with cetyltrimethyl ammonium bromide or sodium dodecylbenzene sulphonate. In A. L. Smith (ed.), Theory and Practice of Emulsion Technology, Academic Press, Norwich, UK, 1976, pp. 281–299.

    Google Scholar 

  16. M. Nakamae, K. Yuki, T. Sato, and H. Maruyama. Preparation of polymer emulsions using a poly(vinyl alcohol) as protective colloid. Colloids Surf. A153:367–372 (1999).

    Google Scholar 

  17. G. O. Yahya, S. K. A. Ali, and E. Z. Hamad. Surface and interfacial activities of hydrophobically modified poly(vinyl alcohol) (PVA). Polymer 37:1183–1188 (1996).

    Google Scholar 

  18. F. Boury, T. Ivanova, I. Panaiotov, J. E. Proust, and A. Bois. and J. Richou. Dynamic properties of poly(DL-lactide) and polyvinyl alcohol monolayers at the air/water and dichloromethane/water interfaces. J. Colloid Interface Sci. 169:380–392 (1995).

    Google Scholar 

  19. K. M. Shakesheff, C. Evora, I. Soriano, and R. Langer. The adsorption of poly(vinyl alcohol) to biodegradable microparticles studied by X-ray Photoelectron Spectroscopy (XPS). J. Colloid Interface Sci. 185:538–547 (1997).

    Google Scholar 

  20. N. Garti. A new approach to improved stability and controlled release in double emulsions, by the use of graft-comb polymeric amphiphiles. Acta Polym. 49:606–616 (1998).

    Google Scholar 

  21. J. Lyklema. Adsorption of polymers and polyelectrolytes. In J. Lyklema (ed.), Fundamentals of Interface and Colloid Science. Vol II . Solid-Liquid Interfaces, Academic Press, Bridgend, Great Britain, 1995, pp.5.1–5.100.

    Google Scholar 

  22. H. Sonntag, B. Ehmke, R. Miller, and L. Knapschinski. Steric stabilization of polyvinyl alcohol adsorbed on silica/water and water/oil interfaces. Adv. Colloid Interface Sci. 16:381–390 (1982).

    Google Scholar 

  23. P. Omarjee, A. Espert, and O. Mondain-Monval. Polymerinduced repulsive forces at solid-liquid and at liquid-liquid interfaces. Langmuir 17:5693–5695 (2001).

    Google Scholar 

  24. W. Li, D. Gersappe, G. H. Ko, M. Asahi, Y. Takashima, and T. Morimoto. Protection of colloidal suspensions with random poly-(vinyl acetate) copolymers. Langmuir 17:3871–3876 (2001).

    Google Scholar 

  25. P. D. Hong, C. M. Chou, and C. H. He. Solvent effects on aggregation behavior of polyvinyl alcohol solutions. Polymer 42: 6105–6112 (2001).

    Google Scholar 

  26. H. Li, W. Zhang, W. Xu, and X. Zhang. Hydrogen bonding governs the elastic properties of poly(vinyl alcohol) in water: singlemolecule force spectroscopic studies of PVA by AFM. Macromolecules 33:465–469 (2000).

    Google Scholar 

  27. K. Lewandowska, D. U. Staszewska, and M. Bohdanecky. The Huggins viscosity coefficient of aqueous solution of poly(vinyl alcohol). Eur. Polym. J. 37:25–32 (2001).

    Google Scholar 

  28. S. W. Lyoo, S. I. Seo, C. B. Ji, H. J. Kim, S. S. Kim, D. H. Ghim, C. B. Kim, and J. Lee. Role of the stereosequences of poly(vinyl alcohol) in the rheological properties of syndiotacticity-rich poly-(vinyl alcohol)/water solutions. J. Appl. Polym. Sci. 88:1858–1863 (2003).

    Google Scholar 

  29. S. Tesch and H. Schubert. Influence of increasing viscosity of the aqueous phase on the short-term stability of protein stabilized emulsions. J. Food Eng. 52:305–312 (2002).

    Google Scholar 

  30. A. Nandi, D. V. Khakhar, and A. Mehra. Coalescence in surfactant-stabilized emulsions subjected to shear flow. Langmuir 17: 2647–2655 (2001).

    Google Scholar 

  31. . R. Morita, R. Honda, and Y. Takahashi. Development of oral controlled release preparations, a PVA swelling controlled release system (SCRS): I. Design of SCRS and its release controlling factor. J. Control. Rel. 63:297–304 (2000).

    Google Scholar 

  32. H. Yang, P. Zhu, C. Peng, S. Ma, Q. Zhu, and C. Fan. Viscometric study of polyvinyl alcohol in NaCl/water solutions ranged from dilute to extremely dilute concentration. Eur. Polym. J. 37:1939–1942 (2001).

    Google Scholar 

  33. L. Dai, K. Ukai, M. S. Shaheen, and K. Yamaura. Gelation of a new hydrogel system of atactic-poly(vinyl alcohol)/NaCl/H2O. Polym. Int. 51:715–720 (2002).

    Google Scholar 

  34. H. Li, W. Zhang, X. Zhang, </del>. Shen, B. Liu, C. Gao, and G. Zou. Single molecule force spectroscopy on poly(vinyl alcohol) by atomic force microscopy. Macromol. Rapid Commun. 19:609–611 (1998).

    Google Scholar 

  35. I. B. Ivanov and P. A. Kralchevsky. Stability of emulsions under equilibrium and dynamic conditions. Colloids Surf. A 128:155–175 (1997).

    Google Scholar 

  36. I. B. I vanov, K. D. Danov, and P. A. Kralchevsky. Flocculation and coalescence of micron-size emulsion droplets. Colloids Surf. A 152:161–182 (1999).

    Google Scholar 

  37. C. A. Miller. Spontaneous emulsification produced by diffusion-A review. Colloids Surf. 29:89–102 (1988).

    Google Scholar 

  38. J. T. Davies and K. E. Ridcal. Interfacial phenomena, 2nd Ed., Academic Press, New York, U.S.A., 1963, pp. 343–450.

    Google Scholar 

  39. D. W. Van Krevelen. Properties of Polymers, 3rd Ed., Elsevier, Amsterdam, Netherlands, 1990, pp. 189–225.

    Google Scholar 

  40. A. Martin, P. Bustamante and A. H. C. Chun. Physical Pharmacy, 4th Ed., Lea & Febiger, Philadelphia, U.S.A., 1993, pp. 556–594.

    Google Scholar 

  41. R. C. Reid, J. M. Prausnitz and B. E. Poling. The Properties of Gases and Liquids, 4th Ed., McGraw-Hill, New York, U.S.A., 1986, pp. 577–631.

    Google Scholar 

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Galindo-Rodriguez, S., Allémann, E., Fessi, H. et al. Physicochemical Parameters Associated with Nanoparticle Formation in the Salting-Out, Emulsification-Diffusion, and Nanoprecipitation Methods. Pharm Res 21, 1428–1439 (2004). https://doi.org/10.1023/B:PHAM.0000036917.75634.be

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