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7 Zeta Potential of Nanosuspensions: 7.1 Background For Nanocrystals
7 Zeta Potential of Nanosuspensions: 7.1 Background For Nanocrystals
Figure 7-1: Stern model of the zeta potential theory showing the course of the potential in the different layers
(upper) and the composition of the different layers (lower).
The zeta potential is determined by measuring the electrophoretic particle velocity in an electrical
field. During the particle movement the diffuse layer is shorn off, hence the particle obtains a
charge due to the loss of the counter ions in the diffuse layer this potential at the plane of shear is
called the zeta potential.
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Figure 7-2: Adsorbed polymer layer shift the plane of shear further away from the particle surface as a
function of the adsorbed layer thickness, protecting the covered part of the diffuse layer against being shorn
off in the electrophoretic zeta potential measurement , thus leading to lower measured zeta potentials (despite
an unchanged surface charge and remaining electrostatic stabilisation)
224
225
zeta potential in mV
60.0
40.0
20.0
0.0
-20.0
-40.0
-60.0
-80.0
0.001
0.01
0.1
10
100
1000
sodium glycocholate
chitosan
Dehyquart CA-A
zeta potential in mV
-10.0
-15.0
-20.0
-25.0
-30.0
-35.0
0.001
0.01
0.1
PLX 407
Tween 80
TPGS
Figure 7-3: Dependence of the zeta potential on the concentration of stabilisers used.
upper: negatively charged surfactants; SDS and sodium glycocholate, positively charged surafactants;
chitosan chloride and Dehyquart.
lower: steric stabilisers; Poloxamer 188 and 407, Tween 80 and p-glycoprotein inhibitor TPGS
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7.6 Influence of pH
Figure 7-4 shows the zeta potential profil of the stock nanosuspension (NS; stabilised with 0.5%
Poloxamer 188) and the suspensions after addition of another 0.5% Poloxamer 188 (NS+ PLX
188 0.5%) and the suspension after addition of another 0.5% Poloxamer 188 and 0.5%
Poloxamer 407). With decreasing pH the electrolyte concentration increases, leading to a reduced
zeta potential. This is even more pronounced because the measured zeta potential is reduced
anyway in case of adsorbed polymers (shift of plane of shear). At low pH values 1 and 2 the zeta
potential is practically zero (i.e. in stomach), that means the nanocrystals are only stabilised by
the steric stabilisation effect. When reaching pH 2, the zeta potential for all Poloxamer mixtures
is around -20mV, sufficient for a stable suspension in case of combined steric and electrostatic
stabilisation. In general the zeta potentials are lower with increasing Poloxamer concentrations in
the nanosuspension, being lowest for Poloxamer 188 and Poloxamer 407 combined stabilised
nanosuspensions.
zeta potential in mV
10.0
0.0
-10.0
-20.0
-30.0
-40.0
1
pH
NS
NS + PLX 188 0.5%
NS + PLX 188 0.5% + PLX 407 0.5%
Figure 7-4: Zeta potential-pH profile of cyclosporine stock nanosuspension NS (stabilised with 0.5% PLX
188) and nanosuspensions after addition of additional PLX 188 0.5% and after addition of a mixture of PLX
188 0.5% + PLX 407 0.5%)
Figure 7-5 shows the nanosuspension after the addition of a mixture of PLX 188 0.5% + SDS 103
M, compared to the original stock suspension (NS) and the stock dispersion NS + PLX 188
0.5%. The concentration of 10-3M SDS was chosen because in previous studies it provided the
highest zeta potential as a function of SDS concentration. The figure clearly shows that SDS
addition had practical no effect ad low pH values of 1 and 2, because the electrolyte
concentration is very high, reducing the thickness of the diffuse layer and the zeta potential.
Some limited effect was seen for SDS addition around pH 5-7 in low electrolyte conditions.
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zeta potential in mV
10.0
0.0
-10.0
-20.0
-30.0
-40.0
1
8
pH
NS
NS + PLX 188 0.5%
NS + PLX 188 0.5% + SDS 10-3M
Figure 7-5: Zeta potential-pH profile of cyclosporine stock nanosuspension NS (stabilised with 0.5% PLX
188) and nanosuspensions after addition of additional PLX 188 0.5% and after addition of a mixture of PLX
188 0.5% + SDS 10-3M
Highest zeta potential values were observed with the nanosuspension co-stabilised with SDS 103
seen in Figure 7-3 (upper). The positive charge of chitosan of around +30mV was very little
influenced by the pH in the pH range from 2-7, thus making it ideal as a stabiliser for the
cyclosporine nanosuspensions. Due to the excellent properties of chitosan Dehyquart was not
further investigated (Figure 7-6).
TPGS showed a pronounced pH dependency, leading to a zeta potential below approximately 10mV at pH 3 and a zeta potential of around 0 at pH 1 and 2 (Figure 7-6). Because TPGS has a
lower molecular weight than the Poloxamers, instabilities in the stomach cannot be excluded.
40.0
zeta potential in mV
30.0
20.0
10.0
0.0
-10.0
-20.0
-30.0
-40.0
1
8
pH
TPGS 1.0%
Chitosan 0.01mol
Figure 7-6: Zeta potential-pH profile of cyclosporine nanosuspensions after addition of additional chitosan
1.0% and after addition of a TPGS 1.0%
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1200
z-average in nm
1100
1000
900
800
700
600
500
1
8
pH
NS
NS + PLX 188 0.5%
NS + PLX 188 0.5% + SDS 10-3M
Figure 7-7: Particle size of nanosuspensions at different pH values adjusted with HCL and NaOH,
respectively, determined by PCS approx. 15min after pH adjustment
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25
20
15
zeta potential in mV
10
5
0
-5
-10
-15
-20
-25
-30
MgCl2
CaCl2
0.9
0.5
0.1
0.9
0.5
0.1
0.9
0.5
NaCl
0.1
0.9
0.5
0.1
-35
AlCl3
SDS
PLX 407
Tween 80
TPGS
Dehyquart CA-A
Figure 7-8: Zeta potentials of nanosuspensions stabilised with additional various stabilisers as a function of
increasing concentration of 1:1 (NaCl), 2:1 (MgCl2, CaCl2) and 3:1 (AlCl3) electrolytes.
zeta potential in mV
-0.7
-1.6
-4.7
-3.4
-10.5
PLX 188
SDS
PLX 407
Tween 80
TPGS
Dehyquart CA-A
Figure 7-9: Zeta potentials of nanosuspensions stabilised with additional various stabilisers in isotonic
sodium chloride solution
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