Coexistence of oil droplets and lipid vesicles in propofol drug products
| Autor: | Yong Wu, Lynn Chen, Xiaoming Xu, Soumyarwit Manna, Jiwen Zheng, Bonhye Koo, Peter Petrochenko, Stephanie Choi, Darby Kozak |
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| Rok vydání: | 2019 |
| Předmět: |
Pharmaceutical Science
02 engineering and technology Fractionation 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Microscopy Electron Transmission Lecithins Particle Size Lipid bilayer Propofol Chromatography High Pressure Liquid Phospholipids Active ingredient Egg lecithin Chromatography Chemistry Vesicle Cryoelectron Microscopy Lipid Droplets 021001 nanoscience & nanotechnology Oil droplet Emulsion lipids (amino acids peptides and proteins) Emulsions 0210 nano-technology Drug carrier Ultracentrifugation |
| Zdroj: | International journal of pharmaceutics. 577 |
| ISSN: | 1873-3476 |
| Popis: | Propofol is intravenously administered oil-in-water emulsion stabilized by egg lecithin phospholipids indicated for the induction and maintenance of general anesthesia or sedation. It is generally assumed to be structurally homogenous as characterized by commonly used dynamic light scattering technique and laser diffraction. However, the excessive amount of egg lecithin phospholipids added to the propofol formulation may, presumably, give rise to additional formation of lipid vesicles (i.e., vesicular structures consisting of a phospholipid bilayer). In this study, we investigate the use of high-resolution cryogenic transmission electron microscopy (cryo-TEM) in morphological characterization of four commercially available propofol drug products. The TEM result, for the first time, reveals that all propofol drug products contain lipid vesicles and oil droplet-lipid vesicle aggregated structures, in addition to oil droplets. Statistical analysis shows the size and ratio of the lipid vesicles varies across four different products. To evaluate the impact of such morphological differences on active pharmaceutical ingredient (API)'s distribution, we separate the lipid vesicle phase from other constituents via ultracentrifuge fractionation and determine the amount of propofol (2,6-diisopropylphenol) using high performance liquid chromatography (HPLC). The results indicate that a nearly negligible amount of API (i.e., NMT 0.25% of labeled content) is present in the lipid vesicles and is thus primarily distributed in the oil phase. As oil droplets are the primary drug carriers and their globule size are similar, the findings of various lipid vesicle composition and sizes among different propofol products do not affect their clinical outcomes. |
| Databáze: | OpenAIRE |
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