Chemistry Reference
In-Depth Information
The formation of a crystalline structure from the adsorption of lipid com-
ponents has been demonstrated on mucosa membrane. Lipid components,
such as GMO and glyceryl monolinoleate (GML), can form cubic phase liquid
crystals when in contact with the aqueous mucosa (Nielsen et al., 1998). The
crystalline phases are formed from the hydration of the lipid components such
that a drug added to the precursor formulation is also incorporated in the
cubic phase formed. Tensiometric measurements show that precursors of the
cubic phase are more mucoadhesive than the cubic phase (Nielsen et al., 1998).
This interesting fi nding suggests that formation of crystalline structure from
lipid components can be a better approach for surfaces with high water content.
An interesting phenomena relating to the formation of a cubic liquid crys-
talline phase in a confi nement between two surfaces is reported in a study
using the interferometric surface force apparatus (SFA) and ellipsometry
(Campos et al., 2002). The study utilized GMO, which has low solubility in
aqueous solution, and, therefore, the solution was equilibrated with an excess
of GMO cubic liquid crystal. GMO was found to adsorb from aqueous solution
to a hydrophobized silica surface as a 2.5-nm monolayer. Surprisingly, the force
versus distance curves between two hydrophobized mica surfaces in saturated
solutions of GMO is characterized by a strong repulsive interaction beneath
surface separation of 40 nm. If suffi cient force is applied, the surfaces can be
brought into (adhesive) contact. Here it should be noted that the surplus of
GMO will fl oat on the surface of the aqueous solution as a fully swollen cubic
phase. This means that any disturbances of the system can cause a phase sepa-
ration of the cubic phase. The confi nement of a mixed solution/dispersion or
a solution/gas close to saturation between two surfaces (in effect forming a
capillary) can produce so-called capillary-induced phase separation (CIPS).
CIPS has been demonstrated for a number of systems, which can drastically
change the forces between the surfaces (Evans and Wennerström, 1999). This
is exactly what can happen in the confi nement between the surfaces, where a
cubic phase is suggested to form between two surfaces in close contact in a
solution saturated with GMO. The repulsive force observed by Campos et al.
(2002) is likely to arise from the compression of the cubic phase GMO, which
is known to be very stiff (Pitzalis et al., 2000).
10.5.3
Formation by Chemical Reactions (e.g., Lipolysis)
In the pioneering in vitro study of lipolysis of a droplet of triglycerides in
an intestine-like environment, Patton and Carey observed, apart from the
initially occurring crystalline phase, a viscous isotropic phase composed
of monoglycerides and fatty acids, which is identical to the one formed in
monoglyceride systems (Patton and Carey, 1979). In excess of bile salts, the
lipolysis products, later defi ned as cubic phase, are rapidly solubilized in
mixed micelles of lipids and bile salts. However, the bile acid amounts in
vivo are not suffi cient to solubilize all lipids after a meal rich in fats, which
implies that the cubic liquid crystalline phases exist in vivo (Lindström et al.,
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