Production Technology

As mentioned earlier, the production of SLNs is performed by dispersing the drug-containing melted lipid in a hot aqueous surfactant solution by stirring and subsequent high-pressure homogenization. The original teaching of the SLN patent by Müller and Lucks is that only lipid concentrations up to a maximum of 30% can be employed; using a higher lipid concentration leads to the formation of creams with a bicoherent structure. Surprisingly, it was found that when even homogenizing concentrations of 70 or 80% lipid, no bicoherent structures were obtained, but definite nanopar-ticles. Therefore, the new NLC application contains—apart from a product claim of a nanostructured lipid particle—a production process claim describing the formation of lipid nanoparticles when employing solid concentrations above 30% up to 95%.

Of course, a lipid concentration of 80% cannot be produced in a one-step production process by high-pressure homogenization. For this, a two-step process is employed. In the first step, a stock lipid nanoparticle dispersion of 60% lipid content is produced. In the second step, melted lipid is added stepwise, and dispersed after each addition by highspeed stirring in the nanoparticulate stock dispersion. The principle of this process is shown in Figure 4. A 1000 g stock dispersion is produced by high-pressure homogeniza-tion containing 600 g of lipid in the form of nanoparticles and 400 g of water (first step). In the next step, an additional 100 g of lipid are added, which means dispersed in the 400 g water, leading to a total of 1100 g particle dispersion, now containing 700 g of lipid particles and still 400 g of water. In the next step, again, 100 g of melted lipid are dispersed in the 400 g of water, leading to a total of 800 g lipid plus still 400 g water, which means that the lipid content increases continuously. The newly added melted lipid is dispersed each time in 400 g water. Repeating this process can produce an 80% lipid nanoparticle dispersion. Of course, parti-

Spray-drying of Compritol-SLN

(a) Spray-drying of Compritol-SLN

10%Compr. 10%Compr. 2.5% Compr. 1%Compr. before spray-drying

Lyophilisation of Compritol-SLN

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