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When poorly water-soluble drugs are formulated in colloidal lipid emulsions, adequate stability of the emulsion must be ensured. The aim of this work was to investigate different aspects related to drug loading in order to gain a better understanding on how drugs affect the stability of phospholipid-stabilised emulsions. To obtain information on emulsion stability, a rapid and reproduceable shaking test was developed. A passive loading approach was applied for drug loading of the commercially available nanoemulsion Lipofundin® MCT/LCT 10% with seven drugs of different charge and localisation tendency within the emulsion system. Localisation of drug molecules in the droplet interface did not generally lead to destabilisation of the emulsion, whereas the charge of the drug was of decisive importance. Aspects such as the drug concentration, its influence on the pH and the impact of zeta potential changes had an influence on emulsion stability as well. Certain destabilising effects of drugs could be counteracted by modification of the pH. Lipofundin® MCT/LCT 10%, passively loaded with propofol, was compared with two commercially available propofol preparations. No negative effect of the passive loading procedure could be detected.

In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to −60 °C.

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