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Review
. 2019 Jan;9(1):4-18.
doi: 10.1016/j.apsb.2018.11.001. Epub 2018 Nov 14.

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles

Jinsong Tao  1 , Shing Fung Chow  2 , Ying Zheng  1
Affiliations
Review

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles

Jinsong Tao et al. Acta Pharm Sin B. 2019 Jan.

Abstract

Nanoparticles are considered to be a powerful approach for the delivery of poorly water-soluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation (FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles, polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer (CIJM), multi-inlet vortex mixer (MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly water-soluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.

Keywords: ACN, acetonitrile; CA 320S Seb, cellulose acetate 320S sebacate; CAP Adp 0.33, cellulose acetate propionate 504-0.2 adipate 0.33; CAP Adp 0.85, cellulose acetate propionate adipate 0.85; CFA, cefuroxime axetil; CIJM, confined impinging jets mixer; CMCAB, carboxymethyl cellulose acetate butyrate; CTACl, cetyltrimethylammonium chloride; DMF, dimethyl formamide; DMSO, dimethyl sulfoxide; DSPE-PEG, distearyl phosphatidyl ethanolamine-poly(ethylene glycol); Dex-PLLA, dextrose-poly(l-lactic acid); FNP, flash nanoprecipitation; Flash nanoprecipitation; HPC, hydroxypropyl cellulose; HPMC, hydroxypropyl methyl cellulose; HPMCAS, hydroxypropyl methylcellulose acetate succinate; MIVM, multi-inlet vortex mixer; Microfluidic mixer device; NaAlg, sodium alginate; NaCMC, carboxymethyl cellulose sodium; Nanoparticles; P(MePEGCA-co-HDCA), poly(methoxy polyethylene glycol cyanoacrylate-co-hexadecyl cyanoacrylate); PAA, poly(acrylic acid); PAH, polyallylamine hydrochloride; PCL, poly(ε-caprolactone); PEG, polyethylene glycol; PEG-PCL, poly(ethylene glycol)-poly(ε-caprolactone); PEG-PLA, poly(ethylene glycol)-poly(lactic acid); PEG-PLGA, poly(ethylene glycol)-poly(lactic-co-glycolic acid); PEG-PS, poly(ethylene glycol)-polystyrene; PEI, polyethyleneimine; PEO-PDLLA, poly(ethylene oxide)-poly(d,l-lactic acid); PLA, poly(lactic acid); PLGA, poly(lactic-co-glycolic acid); PMMA, polymethyl methacrylate; PSS, polyprotomine sulfate; PVA, polyvinyl alcohol; PVP, polyvinyl pyrrolidone; Poorly water-soluble drug; SDS, sodium dodecyl sulfonate; SLS, sodium lauryl sulfate; THF, tetrahydrofuran; TPGS, tocopheryl polyethylene glycol 1000 succinate; ε-PL, ε-polylysine.

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Figures

fx1
Graphical abstract
Fig. 1
Figure 1
La Mer model and schematic diagram of the nanoparticle forming process during the FNP.
Fig. 2
Figure 2
Schematic representation of the process of FNP of organic actives and block copolymers (Reproduced from Ref. with permission. Copyright © 2003 CSIRO Publishing.).
Fig. 3
Figure 3
The relationship between the mixing rate and nanoparticle size in a CIJM (Reproduced from Ref. with permission. Copyright © 2003 CSIRO Publishing.).
Fig. 4
Figure 4
Schematics of confined imping jet mixer (CIJM).
Fig. 5
Figure 5
schematics of multi-inlet vortex mixer (MIVM).
Fig. 6
Figure 6
Schematics of Y-shape microfluidic mixer (A), T-shape microfluidic mixer (B), planar flow focusing mixer (C) and cross-shaped planar flow focusing mixer (D).
See this image and copyright information in PMC

References

    1. Thorat A.A., Dalvi S.V. Liquid antisolvent precipitation and stabilization of nanoparticles of poorly water soluble drugs in aqueous suspensions: recent developments and future perspective. Chem Eng J. 2012;181-182:1–34.
    1. Dahan A., Miller J.M., Hoffman A., Amidon G.E., Amidon G.L. The solubility--permeability interplay in using cyclodextrins as pharmaceutical solubilizers: mechanistic modeling and application to progesterone. J Pharm Sci. 2010;99:2739–2749. - PubMed
    1. Jain N.K., Gupta U. Application of dendrimer–drug complexation in the enhancement of drug solubility and bioavailability. Expert Opin Drug Metab Toxicol. 2008;4:1035–1052. - PubMed
    1. Serajuddin A.T. Salt formation to improve drug solubility. Adv Drug Deliv Rev. 2007;59:603–616. - PubMed
    1. Stella V.J., Nti-Addae K.W. Prodrug strategies to overcome poor water solubility. Adv Drug Deliv Rev. 2007;59:677–694. - PubMed