Applicability of differential scanning calorimetry for the determination of drug concentration in lipid nanoparticlesTreiber, Urška (Avtor) Ahlin Grabnar, Pegi (Mentor) Bunjes, Heike (Komentor) lipid nanoparticles Trimyristin differential scanning calorimetrySince many new drug substances are lipophilic and consequently poorly water soluble, it has become more and more necessary to find new solubilization solutions and adequate delivery formulations. Many different colloidal carrier systems have been developed for such purpose and one among them are lipid nanoparticles. A major concern regarding such formulations is a sufficient stability of their thermodynamically labile colloidal state and thus an adequately extensive characterization is normally made. Beside the determination of particle size, their morphology and zeta potential is an evaluation of the crystallinity and polymorphism also extremely important. For monitoring the latter characteristic differential scanning calorimetry (DSC) is most commonly used. The aim of the thesis work was to investigate if DSC could also be used for other purposes, for example to quantify concentration of drug loaded into lipid nanoparticle formulation. The model system, trimyristin – poloxamer 188 nanoemulsion, was prepared by hot melt homogenization, thoroughly characterized and the chosen lipophilic drug substances (curcumin, propofol, fenofibrate, diazepam and betamethasone valerate) were then passively loaded into the basic nanoemulsion in concentration range expected to be under their saturation limit. The stability of such supercooled nanoemulsion formulation and loaded samples have been regularly checked throughout the entire period of experimental work. To prove a linear correlation between the concentration of drug in the nanoemulsion and the decrease in crystallization temperature (Tcryst) of such loaded sample compared to the unloaded, a very precise and reproducible DSC method had to be developed first. Good experimental conditions were found by comparing two DSC devices and changing several parameters, namely type of crucible, cooling rate and sample volume. At the end DSC device, which allows the use of Mettler crucibles with pin was selected and the sample volume 20 μL and 2.5 Kmin-1 cooling rate were finally chosen for the further measuring of Tcryst. The following investigation with selected DSC method then confirmed the predicted linear correlation between drug concentration and Tcryst for samples loaded with all five drug substances. Additionally the comparison between the chosen drugs was made by converting mass concentration (m/m %) to concentration expressed as the amount of drug substance to the mass of lipid (mmol drug/g lipid). At the end the applicability of the developed DSC method was also tested by determining fenofibrate and diazepam loading kinetics.[U. Treiber]20142020-09-29 14:19:19Diplomsko delo121071UDK: 620.3+66.095(043.2):615.014COBISS_ID: 3679345sl