Table 2.

Methods for producing PLGA based microparticles for sustained-release formulations: Advantages and Disadvantages.

Methods	Schematic diagrams	• Advantages	• Disadvantages	References
Oil-in-water (o/w) emulsion		Simplicity Suitability for temperature-sensitive compounds Control of particle size	Low encapsulation efficiency especially for water-soluble payloads Solvent residuals Low yield, agglomeration of sticky particles	Varde and Pack, 2004
Water-in-oil-in-water (w/o/w) emulsion
Supercritical CO2 (scCO2)		Negligible residual organic solvent	Multiple steps, poor control of particle size, size distribution, and morphology	Falco et al., 2012; Dhanda et al., 2013
Spray drying		Can encapsulate wide range of drugs/peptides/proteins into microparticles without significant loss Final drying step not required One step and reproducible Atomizers (nozzles) eliminate the need for complicated pre-preparation processes and enable continuous manufacture by utilization of liquid feeds via two separate channels	Adhesion of microparticles to inner walls of the spray-dryer Not suitable for temperature-sensitive compounds Difficult to control particle size Low yield, agglomeration of sticky particles	Makadia and Siegel, 2011; Sosnik and Seremeta, 2015; Wan and Yang, 2016
CES (Other modification, such as, coaxial tri-capillary electrospray, Emulsion-coaxial electrospinning)		Nearly 100% encapsulation rate Useful for encapsulating water-soluble molecules Protects biologically active payloads from processing-induced damage Potential to control particle morphology with flexibility and reproducibility for both micro- and nanoparticle size ranges	At early stage; requires further development Standardized protocols and systematic process controls not available as yet Lack of an effective particle collection method; commonly used one-step collection methods cannot facilitate shell hardening, or maintain particle morphology or prevent particle aggregation Lack of a more productive nozzle design	Lee et al., 2011; Viry et al., 2012; Zhang et al., 2012; Zamani et al., 2014; Yuan et al., 2015
Microfluidics (Other modification, such as, capillary microfluidics coupled with solvent evaporation)		Ultra-small quantities of reagents needed Precise control over drug release rate, drug loading efficiency, particle shell thickness, particle shape and size Multiple components are easily generated using single-step emulsification	A time-consuming method as single drops are generated one at a time	Demello, 2006; Hung et al., 2010; Xie et al., 2012; Cho and Yoo, 2015; Leon et al., 2015
Hydrogel template		Higher drug loading and sustained release profiles	novel technique not widely used as yet	Acharya et al., 2010a,b; Malavia et al., 2015

CES, Coaxial electrospray; PLGA, Poly(lactic-co-glycolic acid).