cipitation is also called solvent displacement method or interfacial precipitation method [143-148] .It depends on the precipitation of a preformed polymer from an organic solution and the diffusion of the organic solvent in the aqueous phase either in the presence or absence of a surfactant [143, 149-151].
The main principle of this technique is based on the interfacial deposition of a polymer after displacement of a semi polar solvent, miscible with water, from a lipophilic solution. Rapid diffusion of the solvent into non-solvent phase results in the decrease of interfacial tension between the two phases, which increases the surface area and causes the formation of small droplets of organic solvent [143, 152].
Nanoprecipitation system composed of three basic components: the polymer (synthetic, semi synthetic or natural), the polymer solvent and the non-solvent of the polymer. Organic solvent (i.e., Ethanol, acetone, hexane, methylene chloride or dioxane) which is miscible in water and can be easily removed by evaporation is chosen as polymer solvent. Because of this reason, acetone is considered to be the most commonly used polymer solvent in this method [143,153, 154].
Sometimes, it consists of binary solvent blends, acetone with small volume of water [155], blends of acetone with ethanol [156-158] and methanol [159].
The polymers commonly used are biodegradable polyesters, especially poly (Ɛ-caprolactone) (PCL) [160-164], polylactide (PLA) [165, 166] and poly (lactide-co-glycolide) (PLGA) [167, 168]. Eudragit [156] can also be used as many other polymers such as polyalkylcyanoacrylate (PACA) [169-171].
Natural polymers such as allylic starch [172], dextran ester [173], were also used ,though synthetic polymers have higher purity and better reproducibility than natural polymers [174]. On the other hand, some polymers are PEG copolymerized in order to decrease nanoparticle recognition by the reticular endothelial system [159].
PNP characteristics are influenced by the nature and concentration of their components [162, 164]. The key variables determining the success of the method and affecting the physicochemical properties of the PNP are those associated with the conditions of adding the organic phase to the aqueous phase, such as organic phase injection rate, aqueous phase agitation rate, the method of organic phase addition and the organic phase to aqueous phase ratio.
Lince et al.,2008 [175] indicated that the process of particle formation in the nanoprecipitation method includes three stages: nucleation, growth and aggregation. The separation between the nucleation and the growth stages is the key factor for formation of uniform particles. Ideally, operating conditions should allow a high nucleation rate strongly dependent on super saturation and low growth rate.