Biomedical Engineering Reference
In-Depth Information
Table 3
List of commonly used organic solvents for dissolving the polymers
Concentration limit
in pharmaceutical
formulations (ppm
a,b
) Boiling point (
C) Miscibility with water
Solvents
Solvent class
Dichloromethane 2
600
40
Immiscible
Chloroform
2
60
61
Immiscible
Ethyl acetate 3 5,000 77 Immiscible
As per ICH guidelines for residual solvents Q3C (R4) and United States Pharmacopeia, class 2 solvents are solvents to be
limited in pharmaceutical products and class 3 solvents are solvents with low toxic potential
a
United States Pharmacopeia
b
Values according to ICH guidelines Q3C (R4)
7. The solvent choice for the emulsion solvent evaporation
method should be based on the following criteria:
(a) Polymer should be soluble in the solvent
(b) Solvent should be immiscible with the aqueous phase
(c) Solvent should be completely and easily removed
Solvents that can be employed apart from DCM are
ethyl acetate and chloroform [
9
]. Table
3
lists the solvents
that can be employed for dissolving the polymers and their
physical properties.
8. Surfactants function as emulsifiers by adsorbing on the surface
of the oil globules and preventing them from aggregating [
47
].
PVA has been reported to aid in nanoparticle formation at
concentrations as low as 0.1 % w/v [
48
]. However, the higher
the PVA concentration used, the smaller is the size of the
nanoparticles obtained [
49
,
50
]. At higher PVA concentration,
more number of surfactant molecules would be adsorbed on
the particle surface, thereby preventing the oil droplets from
coalescing. PVA at 2 % w/v has been found to give rise to stable
nanoparticles with particle size in the range of ~200-500 nm by
the methods described.
9. The PVA solution should be stored at 4
C.
10. The phase ratio (organic to aqueous solvent ratio) may influence
the size of the nanoparticles [
48
]. In general, a ratio of 1:10 of
organic/aqueous phase produced nanoparticles of ~350 nm size
when prepared by the method described [
16
].
11. Strong agitation force is required to reduce the droplet size for
forming a stable emulsion. The emulsification step is a key
aspect of the emulsion solvent evaporation method because
the emulsion droplet size is directly related to the final nano-
particle size [
9
]. The higher the sonication power input and
longer
the sonication time,
the smaller
the particle size
achieved [
47
,
49
].
