Chemistry Reference
In-Depth Information
(a)
(b)
100
90
80
70
60
50
40
30
20
10
0
1×10
4
8×10
4
6×10
4
4×10
4
2×10
4
pH2
pH7
pH2
pH7
0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
0
20
40 60
Time [h]
80
100
Time
0.5
[h
0.5
]
Figure 8.18
pH-induced changes in the release of phloroglucinol from the reverse
bicontinuous cubic and hexagonal phases at 37°C: (a) Phloroglucinol released from the
bicontinuous cubic phase at pH 7 (
) and reverse hexagonal phase at pH 2 (
) plotted
against time. (b) Moles released per unit area plotted against the square root of time,
illustrating the different diffusion-controlled behaviors in the two mesophases (Negrini
and Mezzenga, 2011 ).
This order-order transition can be explained by the presence of the ioniz-
able carboxylic group of the linoleic acid (intrinsic p
K
a
5). The linoleic acid
is negatively charged at pH 7; the electrostatic repulsions between the nega-
tively charged head groups stabilize the Im3m bicontinuous cubic phase. When
the pH decreases below the p
K
a
value, the carboxyl group reprotonates to a
large extent, the surface charge density on the water channels at the water-
lipid interface decreases, and the linoleic acid became highly hydrophobic,
acting as an oil and stabilizing the hexagonal phase at 37°C.
This order-order transition is well-rationalized by the concept of the CPP
expressed as
v
/
Al
, which is the ratio between the volume of the hydrophobic
lipid tail,
v
, and the product of the cross-sectional lipid head area,
A
, and the
lipid chain length,
l
. When linoleic acid is deprotonated (pH 7), the effective
area
A
is large because of the electrostatic repulsive interactions among dif-
ferent lipid heads. When, however, the linoleic acid is mostly neutral (pH 2),
A
decreases and the CPP increases, promoting the transition from fl at to
reverse (water-in-oil) interfaces and inducing a bicontinuous cubic
∼
→
reverse
columnar hexagonal transition.
In vitro release studies were carried out fi rst to establish the infl uence of
the liquid crystalline symmetry on the release behavior. Figure 8.18a illustrates
the drug release profi les from the liquid crystalline matrices, plotted as a per-
centage of the released drug against time. As can be observed, the release from
Im3m is much more rapid and is nearly completed after 20 h; at this time, H
II
has not yet released half of the initially loaded drug.
In Figure 8.18b the profi les of drug released are plotted against the square
root of time; the linear behavior confi rms the Fickian diffusion release.
Using the Higuchi equation, the diffusion coeffi cients are calculated to be
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