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Delivering Actives via Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Part I
By: Johann W. Wiechers, PhD, JW Solutions, and Eliana B. Souto
Posted: September 29, 2010, from the October 2010 issue of Cosmetics & Toiletries.
- Figure 1. The differences between SLNs and NLCs
- Figure 2. A schematic overview of both the hot and cold homogenization
- Figure 3. The lipid/active ratio will determine the SLN/NLC produced
- Figure 4. The effect of adding chemically different lipids to a pure lipid
- Figure 5. Selection criteria of lipid materials for SLNs and NLCs
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Actives having higher water solubilities tend to create Type II SLNs/NLCs. If the solubility of the active in water increases at elevated water temperatures, a reasonable to substantial amount of active will escape to the water phase. When the temperature is subsequently lowered—and with it the solubility of the active in the water phase, the active ingredient will partition back into the partially formed nanoparticles. Therefore, the outer layer will be active-enriched on the outside, i.e., a Type II SLN or NLC.
The SLN/NLC type is important because it determines the release characteristics of the particle. Type I SLNs and NLCs (see Figure 3) give a sustained, constant and relatively long release of active. Type II SLNs/NLCs deliver a relatively short, burst release of active. Finally, Type III SLNs/NLCs provide a delayed, relatively high release of active. It is therefore critical to identify the optimal ratio between lipid and active ingredient; this is addressed later in this article. However, the following general rule may save the formulator time: if Type I SLNs/NLCs are desired, note that cold high pressure homogenization will always yield Type I particles.
Solvent emulsification and evaporation: Solvent emulsification and evaporation is another production method for SLNs and NLCs but it is a rather unusual and less popular method due to the use of organic solvents. The oil phase contains lipid as well as organic solvent. The organic solvent is removed under reduced pressure (40–60 mbar), resulting in particle sizes that are dependent upon the surfactant/co-surfactant blend. The advantage of this method is that hardly any thermal stress is applied to any of the chemicals in the formulation.
Microemulsion method: A fourth process is the microemulsion method, which is said to not require energy. In this method, one starts with a hot transparent o/w-microemulsion that is quickly diluted into cold water (2–3°C) in a ratio of 1/25 to 1/50 (microemulsion/water). The shock in temperature causes the lipid to solidify and in this way, a rather low yield SLN/NLC preparation is obtained. The yield is always low due to the strong dilution step of the microemulsion with cold water.
For more information on the methods described here, readers may refer to Reference 7 and the references therein. The production method chosen will depend on variables such as the thermolability of the active and the particle size required for the end product.