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.

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Waxes: The available information about the influence of waxes on the behavior of SLNs is much sparser. Jenna and Gohla compared SLNs made of wax and glycerides and concluded that SLNs based on glycerides such as glyceryl monostearate and glyceryl behenate showed good drug encapsulation but poor physical stability, while SLNs based on wax such as beeswax and cetyl palmitate showed the opposite.¹⁴ The waxes were clearly more crystalline than the lipids, but later research showed that careful mixing of the wax with other lipids could reduce crystallinity. For instance, Attama and Müller-Goymann showed that the crystallinity of beeswax was reduced by the inclusion of heterolipids like phosphatidyl choline^d or homolipids like goat fat^e.¹

General criteria: The general purpose of SLNs and NLCs is to deliver lipophilic active ingredients and APIs into the skin. To achieve this, the entrapment efficiency (EE%) and the loading capacity (LC%) are important. These are determined by the capability of the lipid phase to dissolve the active at 80°C as well as the crystallization behavior during cooling, described above. Mixing very different lipids leads to imperfections in the crystal structure, allowing for a higher LC% but also potentially causing supercooling due to the difference between melting and crystallization temperatures.

The level of supercooling is different for each lipid and can be easily assessed by DSC. When working with pure lipids such as triacylglycerols having a high melting point and a high crystallization temperature, the addition of lipid molecules with small chain length will decrease the temperatures of both phenomena. This means that the amount of supercooling may increase; i.e., the difference between the melting and crystallization temperatures may be increased (see Figure 4).

This figure illustrates the impact of the chemical difference between a pure lipid and an added lipid. Looking from the left to the right of the graph, the chemical difference between the pure lipid and the added lipid increases. The opposite is also valid; the addition of long-chain fatty molecules to lipid materials of low crystallization temperatures decreases the amount of supercooling. During preparation, the emulsified dispersion must be cooled below the critical crystallization temperature of the lipid materials, i.e. much below their melting temperature, in order to crystallize and obtain solid lipid particles. If this critical temperature is not reached, the particles remain in the liquid state and an emulsion of supercooled, liquid droplets is obtained rather than the desired SLN or NLC dispersion.8 As a consequence, all the benefits of SLNs and NLCs are lost since such systems no longer offer the enhanced physical and chemical stability above o/w emulsions.

All the above described scientific background is summarized in two schematics. In Figure 5a, the influence of the crystallinity state of the lipids, which can be modulated via the choice of lipid, on the efficacy of SLNs and NLCs as skin delivery systems is shown. In Figure 5b, some practical experiments that assist in selecting the right lipids are indicated. The formulator must first decide whether SLNs or NLCs will be developed. In the majority of cases, the choice will be for NLCs due to their higher LC%. Then, a couple of suitable lipids are selected based on high and low solubilities for the active ingredient (see Figure 5b). Therefore, solubility experiments are performed at 80°C in which the chemical stability of the active ingredient is also measured. Wherever possible, it is recommended to use hot high pressure homogenization but for this process, it is essential that the active ingredient is not thermolabile.