Nano-formulation Technologies

POLYMERS

  • Eudragits are amorphous polymers having glass transition temperatures between 9 to > 150oC.
  • Eudragits are non-biodegradable, nonabsorbable, and nontoxic.
  • Anionic Eudragit L dissolves at pH > 6 and is used for enteric coating.
  • Eudragit S, soluble at pH > 7 is used for colon targeting.
  • Studies in human volunteers have confirmed that pH drops from 7.0 at terminal ileum to 6.0 at ascending colon, and Eudragit S based systems sometimes fail to release the drug. To overcome the shortcoming, combination of Eudragit S and Eudragit L which ensures drug release at pH < 7 has been advocated.
  • RL and RS, having quaternary ammonium groups, are water insoluble, but swellable/permeable polymers which are suitable for the sustained release film coating applications.
  • Cationic Eudragit E, insoluble at pH ≥ 5, can prevent drug release in saliva and finds application in taste masking.

When encapsulating hydrophobic compounds, two of the most commonly used techniques are- (1) Nanoprecipitation technique (2) Emulsification-solvent evaporation technique.

Nanoprecipitation(solvent displacement)technique

  • In nanoprecipitation (solvent displacement)method rapid diffusion of the organic phase out of the polymer phase into the external aqueous phase leads to the formation of nanoparticles(NPs).
  • NPs are formed in one step.
  • Nanoprecipitation, involves the use of miscible solvents (Acetone more than 100 mg/ml in water).
  • Its advantages include simplicity, good reproducibility, and low energy input.
  • After the NPs formulation with most techniques, some potentially toxic impurities such as organic solvents, surfactant excess, residual monomers, and large polymer aggregates must be eliminated. Some of the most common particle purification methods for laboratory scale include dialysis, gel filtration, evaporation under reduced pressure, and ultracentrifugation.

Emulsion-evaporation technique

  • The emulsification technique is based in a mixture of a volatile non-water miscible solvent and an aqueous solution, which are emulsified by the application of high shear force.
  • Then the volatile solvent is evaporated, forming in the process the NP.
  • This method is advantageous because it is nontoxic, rapid in reaction rate, and produces very small particles.
  • Nevertheless, a disadvantage in the technique is the standardization for each specific drug, the high energy used in the process, which could affect the stability of certain drugs.

Emulsion solvent diffusion technique-partially water miscible organic solvent((Ethyl acetate 50-100 mg/ml in water).

Emulsion solvent evaporation technique- water immiscible organic solvent.(Methylene chloride 10-50 mg/ml in water)

REFERENCES