The encapsulation efficiency of the microparticle or microcapsule or microsphere will be affected by different parameters.

Factors influencing encapsulation efficiency

High solubility of polymer in organic solvent Slow solidification of microparticle Low encapsulation efficiency
Low solubility of organic solvent in water
Low concentration of polymer
High DP/CP ratio
Slow solvent removal

Low solubility of polymer in organic solvent Fast solidification of microparticle High encapsulation efficiency
High solubility of organic solvent in water
High concentration of polymer
Low DP/CP ratio
Fast solvent removal

Solubility of polymer in the organic solvent

A lower molecular weight polymer had a higher solubility in methylene chloride than a higher molecular weight polymer. End-capped polymers, which were more hydrophobic than non-end-capped polymers of the same molecular weight and component ratio, were more soluble in methylene chloride.

Diffusion of drugs into the continuous phase mostly occurred during the first 10 minutes of emulsification; therefore, as the time the polymer phase stayed in the non-solidified (semi-solid) state was extended, encapsulation efficiency became relatively low.

Polymers having relatively high solubilities in methylene chloride took longer to solidify and resulted in low encapsulation efficiencies, and vice versa. Particle size and bulk density also varied according to the polymer. Since polymers having higher solubilities in methylene chloride stayed longer in the semi-solid state, the dispersed phase became more concentrated before it completely solidified, resulting in denser microparticles.

Solubility of organic solvent in water

Methylene chloride resulted in a higher encapsulation efficiency as compared with chloroform or benzene, even though methylene chloride was a better solvent for poly (lactic acid) (PLA) than the others. Methylene chloride is more soluble in water than chloroform or benzene. The ‘high’ solubility allowed relatively fast mass-transfer between the dispersed and the continuous phases and led to fast precipitation of the polymer. The significance of solubility of the organic solvent in water was also confirmed by the fact that the addition of water-miscible co-solvents such as acetone, methanol, ethyl acetate, or dimethyl sulfoxide (DMSO), contributed to increase of the encapsulation efficiency.

In order to explain the low encapsulation efficiency obtained with benzene, the benzene required a larger amount of water (non-solvent) than methylene chloride for precipitation of the polymer, and the drug was lost due to the delayed solidification. However, given that benzene is a poorer solvent than methylene chloride for a PLA polymer, this argument does not agree with the widely spread idea that a poor solvent requires a smaller amount of non-solvent to precipitate a polymer. In fact, there could have been a better explanation if they had considered that the delayed solidification was due to the low solubility of benzene in water: As a poor solvent for a PLA polymer, benzene requires only a small amount of non-solvent for complete solidification of the polymer. However, since benzene can dissolve only a tiny fraction of water, it takes much longer to uptake water into the dispersed phase.

That is, while solubility of a polymer in an organic solvent governs the quantity of a nonsolvent required in precipitating a polymer, solubility of the organic solvent in the non-solvent limits diffusion of the non-solvent into the polymer phase. Thus, when a cosolvent system is involved, both solubility of a polymer in a solvent and solubility of the solvent in a non-solvent participate in determining the solidification rate of the dispersed phase.

Concentration of the polymer
  • Encapsulation efficiency increases with increasing polymer.
  • High viscosity and fast solidification of the dispersed phase contributed to reducing porosity of the microparticles as well.
The contribution of a high polymer concentration to the encapsulation efficiency can be interpreted in two ways :
  1. in highly concentrated: the polymer precipitates faster on the surface of the dispersed phase and prevents drug diffusion across the phase boundary.
  2. the high concentration increases viscosity of the solution and delays the drug diffusion within the polymer droplets.
Ratio of dispersed phase to continuous phase (DP/ CP ratio)
  • Encapsulation efficiency and particle size increase as the volume of the continuous phase increases.
  • It is likely that a large volume of continuous phase provides a high concentration gradient of the organic solvent across the phase boundary by diluting the solvent, leading to fast solidification of the microparticles.
Rate of solvent removal

In the emulsion-solvent evaporation/extraction method, the solvent can be removed by (i) evaporation, in which the solvent is evaporated around its boiling point or (ii) extraction into the continuous phase. The rate of solvent removal can be controlled by the temperature ramp or the evaporation temperature in the former and by the volume of the dilution medium in the latter.

Interaction between drug and polymer
  • Interaction between protein and polymer contributes to increasing encapsulation efficiency.
  • Generally, proteins are capable of ionic interactions and are better encapsulated within polymers that carry free carboxylic end groups than the end-capped polymers.
  • On the other hand, if hydrophobic interaction is a dominant force between the protein and the polymer, relatively hydrophobic end-capped polymers are more advantageous in increasing encapsulation efficiency.
Solubility of drug in continuous phase
  • Drug loss into the continuous phase occurs while the dispersed phase stays in a transitional, semi-solid state.
  • If the solubility of the drug in the continuous phase is higher than in the dispersed phase, the drug will easily diffuse into the continuous phase during this stage.
Molecular weight of the polymer

The encapsulation efficiency of the microspheres improved as the polymer concentration increase in oil phase and PVA concentration decreased in aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30°C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.