Solvent Evaporation

Solvent evaporation is a classical method to produce microcapsules of the monolythic type [113, 114]. The manufacturing method can be modified to produce nanoparticles. In contrast to the in-situ polymerization processes mentioned in the previous sections, for solvent polymerization, a preformed polymer is used, usually poly(lactic acid) or poly(lactic-co-glycolic acid) [115-135, 139-144] or poly(e-caprolactone) [119, 128-130]. The ratio between poly(lactic acid) and poly(glycolic acid) governs the biodegradation rate. The polymer is dissolved in an organic solvent. The drug also is contained in this solvent and may be present in the form of a solution or a fine dispersion, or it may be dissolved in water and then emulsified in the organic medium. As the next step, this organic solution or mixture is emulsified in an aqueous medium to form a O/W (oil in water) emulsion. After emulsification the organic liquid is evaporated under reduced pressure or by spray drying. This then leads to the formation of the solid polymer particles.

In order to form nanoparticles by the solvent evaporation process, compared to normal microcapsules much larger amounts of emulsifiers such as poloxamers [115], poloxa-mines [135], polysorbates [115, 132, 133], sodium lauryl sulfate [115], sodium dodecyl sulfate, poly(vinyl acetate) [118], polyvinyl alcohol) [120, 124-126, 131], albumin [121-126], gelatin [117, 127], etc., plus the employment of high sheer homogenizers or extensive ultrasoniction are necessary in order to form the necessary small (nano)particle size. Since this process is kinetically controlled, the resulting particle size distribution is much broader than after emulsion polymerization. Besides the poly(lactates) other polymers have been used for this process including polyacrylates [136], ethyl cellulose, and poly(B-hydroxybutyrate) [137, 138]. Some of the latter polymers, such as Eudragit® RL or RS and ethyl cellulose, even did not require the use of additional emulsifiers or surfactants due to their amphiphilic properties [136]. In some cases a water soluble organic solvent such as acetone may be added which aids in dispersion of the polymer. If these amounts are relatively minor [139-142] the formation of rather homogeneous monolithic particles prevails; higher amounts lead to formation of nanocapsules. This process is called solvent deposition.

The solvent evaporation process also may be used to encapsulate materials in the form of a double emulsion [143]. A very good review about solvent evaporation and related processes is given by Arshady [144].

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