Composition and Structure - Lipid Nanoparticles: Production, Characterization and Stability - page 17

2.2.2 Drug-Enriched Core Model
A drug-enriched core model is obtained when the recrystallization mechanism
is the opposite of that described for the drug-enriched shell model. Figure 2.2 b
shows a schematic representation of a drug-enriched core model. This morphology
is obtained when the drug has a tendency to crystallize prior to the lipid. The drug
is solubilized in the lipid melt close to its saturation solubility. Subsequent cool-
ing of the lipid emulsion causes super-saturation of the drug in the lipid melt; this
leads to the drug recrystallizing prior to lipid recrystallization. Additional cooling
leads to lipid recrystallization that forms a membrane around the already crystal-
lized drug-enriched core. This structural model is suitable for drugs that require
prolonged release over a period of time, governed by Fick's law of diffusion
(Müller et al. 2002b ).
2.2.3 Solid Solution Model
A solid solution model, also referred to as the homogenous matrix model, is
obtained when the drug is homogenously dispersed within the lipid matrix in
molecules or amorphous clusters. This model is usually described for lipid nan-
oparticles prepared by a cold homogenization technique, or when highly lipo-
philic drugs are incorporated such that a hot homogenization technique can be
employed without the use of surfactants or drug-solubilizing molecules. When a
cold homogenization technique is employed, the solubilized drug is dispersed in
the bulk lipid. When subjected to high pressure homogenization, mechanical agi-
tation leads to the formation of lipid nanoparticles with a homogenous matrix.
A similar result is obtained when the lipid droplets produced by a hot homog-
enization technique are rapidly cooled; droplets tend to crystallize and there is
no phase separation between the drug and the lipid. Such models are suitable for
incorporation of drugs that exhibit prolonged release from particles (Muchow
et al. 2008 ). An example of such a model is a prednisolone-loaded SLN sys-
tem that exhibits slow release of prednisolone, usually from 1 day to 6 weeks
(Jenning and Gohla 2000 ).
2.3 Structure of Nanostructured Lipid Carriers
Like SLNs, NLCs have been proposed to possess three different morphologies,
based on the location of incorporated drug molecules (Jenning et al. 2000a , b , c )
• NLC type I or “imperfect crystal” type
• NLC type II or “multiple” type
• NLC type III or “amorphous” type