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| Nanoencapsulation | Particular features | Major issues and limitation |
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w/o phase separation | High EE% for water-soluble drugs; a phase inducer is used for nanoparticle hardening | Handling and disposal of oil; difficulty in controlling coacervation; relatively large-sized nanoparticles |
| w1/o/w2 emulsion | A well-established process for water-soluble drugs | Poor drug EE%; strategies are needed for improving drug EE%; limited drug payload; drug instablization during emulsification |
| HIP technique | High EE% for water-soluble drugs | Toxic residual ionic surfactants in nanoparticles; alternatives to ionic surfactants are recommended for complexation |
| o/w solvent evaporation | A platform easily adapted for hydrophobic drugs | Use of volatile halogenated organic solvents; solvent toxicity; residual solvent content |
| o/w solvent extraction | A well-established technique for hydrophobic drugs; a nonhalogenated solvent is used | Generation of large quantities of waste-stream; incomplete solvent removal; nanoparticle aggregation |
| o1/o2 emulsion | A preparation method for water-insoluble drugs; processing solvents are nonhalogenated | Disposal and/or recycling of waste oil; poor EE% caused by drug partition to o2 |
| o/w salting-out | Moderate EE% for hydrophobic drugs; water-miscible, nonhalogenated solvent; low-energy mixing device | Use of large quantities of salting-out agents (e.g., salts/electrolytes); recycling of salts/electrolytes |
| Nanoprecipitation | A water-miscible, nonhalogenated solvent; a single-step process for loading hydrophobic drugs; low-energy mixing device; smaller nanoparticle size | A narrow Ouzo region for nanoparticle formation; a polymeric concentration of a dispersed phase is low; nanoparticle aggregation due to incomplete solvent removal |
| SESD | Modified nanoprecipitation for hydrophobic drugs | A binary solvent mixture containing a halogenated one |
| Membrane emulsification | Low-energy mixing device; homogeneous nanoparticle population | Membrane properties decide nanoparticle quality; relatively bigger nanoparticle sizes (e.g., ≥200 nm) |
| Microfluidic technique | Precise control over nanoparticle formation; high drug EE% for various types of drugs; multiple drug loads; low-energy mixing device | Scalability; limitation in commercial scale production |
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