Table 1.

Merits and drawbacks associated with microsphere fabrication methods along with their various process parameters that influence microsphere characteristics

Microsphere fabrication method	Process parameters that influence microsphere properties	Advantages	Disadvantages	References
Emulsion-solvent extraction	Homogenization speed Viscosity/concentration and composition of the “oil” phase Stabilizer concentration Volume ratio of “oil” and “water” phases	Simple method that can be easily set up Can be easily tailored to intended application Can be used to encapsulate large hydrophilic molecules such as DNA	Batch operation increases the cost of commercial production of microspheres Poor control over microsphere size Yields microspheres with high polydispersity Poor encapsulation efficiency of hydrophilic bioactive factors Residual solvent toxicity	20, 33, 35, 51, 56
Precision particle fabrication (PPF)	Viscosity/concentration and composition of the oil phase Stabilizer concentration Polymer flow rate Carrier flow rate Vibration frequency	Fabricated microspheres have low polydispersity Reproducibility among batches Allows precise and instantaneous control over microsphere size May be used for natural materials (with some modifications)	Requires complex apparatus and control systems Increase in polydispersity with small microsphere size	59–61
Thermally induced phase separation	Viscosity/concentration and composition of the oil phase Solvent composition Cooling temperature/rate Needle size (syringe/needle droplet formation) Nozzle size (piezoelectric nozzle droplet formation) Vibration frequency (piezoelectric nozzle droplet formation)	Both synthetic and natural materials can be used Fabricated microspheres are inherently porous Rapid encapsulation More control over microsphere size compared with solvent extraction	Laborious as it entails multiple steps Coalescence of microspheres is an issue Poor control over microsphere size compared with PPF	58, 67