A Critical Appraisal of Solubility Enhancement Techniques of Polyphenols

Table 2

Strategies to improve solubility of polyphenols.

Method	Procedure	Advantages	Disadvantages	Example	Reference
Nanoparticles					[16–18]
Evaporative precipitation into aqueous solution	Spraying of drug solution through an atomizer into an aqueous solution containing stabilizer at high temperature.	High dissolution rate, high surface area, enhanced wettability.	Require stabilizers, lack of controlled release, not suitable for thermolabile drugs	Nanosuspension of quercetin	[45]
High pressure homogenization	Precipitation of drug by addition of antisolvent in the drug solution leading to formation of unstable form of drug which is stabilized by means of single/repeated application of high energy followed by thermal relaxation (annealing).	Reduced particle size, enhanced dissolution, no crystal growth	Long processing time, introduction of impurities, high energy requirements, chemical degradation	Nanosuspension of quercetin	[45]
Antisolvent method
Antisolvent; precipitation using; a syringe pump	Addition of antisolvent to a solution of drug and solvent at a particular flow rate under constant stirring leading to precipitation of drug which is then filtered to collect nanoparticles.	Reduced particle size, high dissolution rate, high surface area, reduced crystallinity, faster onset of action	Contamination due to filtration	Nanoparticles of hesperetin	[65]
Evaporative; precipitation of; nanosuspension	Mixing of a water miscible solvent containing drug with an antisolvent followed by evaporation of solvents.	Decreased particle size, enhanced surface area, improved dissolution	Particle growth due to remaining organic solvent in suspension	Curcumin nanoparticles	[92]
Supercritical; antisolvent; method	Precipitation of drug from drug solution by mixing it with a compressed fluid at its supercritical conditions. Diffusion of solvent into antisolvent phase leads to drug precipitation due to low solubility of drug in antisolvent.	High product purity, controlled crystal polymorphism, possible processing of thermolabile molecules, single step process	Toxicity and flammability of solvents, poor control of particle morphology, incomplete removal of residual solvent	Apigenin nanocrystals	[55]
Solid dispersion	Formation of eutectic mixtures of drugs with hydrophilic carriers by melting their physical mixtures	Particle size reduction, improved wettability, enhanced dissolution, higher porosity	Decrease in dissolution on aging, crystal growth upon moisture absorption, demixing, phase separation	Solid dispersion of ellagic acid	[19–21, 37]
Self-microemulsifying drug delivery systems	Gentle mixing of drug, oil, surfactant, and cosurfactant in aqueous media leading to formation of o/w microemulsion of drug droplets with mean droplet size <100 nm.	Higher bioavailability, improved absorption, oral administration using gelatin capsules	Surfactant toxicity, tedious manufacturing method, interaction with capsule shell	Curcumin	[22, 23, 96]