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Physical Stability due to Changes in Colloidal Lipid Dispersion

Ostwald Ripening

In an SLN suspension, the smaller particles can dissolve preferentially when compared with large particles in the suspension medium. The dissolved lipid then deposits on the larger particulate surfaces, thereby resulting in a growth in the particle size of the larger particles at the expense of the smaller particles. This phenomenon is called Ostwald ripening and is also seen in emulsions, causing an increase in the droplet size of the dispersed phase. SLNs are in general resistant to coalescence but are prone to creaming or gelling due to particle collision [115]. Ostwald ripening can be partially inhibited by narrowing particle size distribution, which minimizes the saturation solubility difference and drug concentration gradients within the medium. Stabilizers can reduce the interfacial tension between the solid particles and liquid medium, thereby preventing Ostwald ripening. Ostwald ripening can be mitigated by stabilizers as long as they do not enhance the drug solubility [119,120]. It depends on the granulometry of particles, in which species flux occurs from small to large droplets via the continuous phase.

Coalescence

Coalescence is an irreversible rupture of the emulsion resulting in phase separation. SLN dispersions tend to cream or gel after particle contact. By contrast, rigid solid particles are expected to be stable against coalescence. Coalescence occurs when two or more droplets merge to form a single larger droplet. This process leads to an irreversible breakdown, referred to as cracking of an emulsion [121]. In the absence of a primary maximum, rapid aggregation can take place, leading to the formation of a strong, irreversible aggregated structure. A network of three-dimensional aggregates with interconnections eventually fuses into a compact pack of particles, causing an irreversible caking of the dispersion [121].

 
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