Premium
Formulation and preparation of a stable intravenous disulfiram‐loaded lipid emulsion
Author(s) -
Chen Xi,
Zhang Ling,
Hu Xi,
Lin Xia,
Zhang Yu,
Tang Xing
Publication year - 2015
Publication title -
european journal of lipid science and technology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.614
H-Index - 94
eISSN - 1438-9312
pISSN - 1438-7697
DOI - 10.1002/ejlt.201400278
Subject(s) - chemistry , disulfiram , diethylamine , lecithin , lipid peroxidation , chromatography , emulsion , degradation (telecommunications) , nuclear chemistry , drug , organic chemistry , pharmacology , biochemistry , antioxidant , medicine , telecommunications , computer science
In this study, a disulfiram‐loaded lipid emulsion (DSF‐LE) was prepared to improve its clinical application in cancer treatment. DSF‐LEs were characterized with regard to their visual appearance, particle size distribution, pH values, and percentage drug degradation. However, it was found that DSF‐LEs had poor chemical stability, which might have been affected by the pH values and lecithin used in our previous study. Buffer salts and CO 2 were used respectively to control the pH, and a significant reduction in DSF degradation in the acceleration test was observed when CO 2 was used as a protective gas. Investigations of naturally‐extracted and synthetic lecithins showed that lecithin contained more phosphatidylethanolamine (PE), causing more degradation of DSF due to its higher peroxidation. As far as the degradation mechanism was concerned, it was speculated that free radicals generated during the peroxidation process of unsaturated acyl‐groups of lecithin could react with DSF to produce unstable diethyldithiocarbamic acid (DDC), which readily broke down into CS 2 and diethylamine. Diethylamine is an alkaline compound that can increase the pH of DSF‐LEs, leading to the further degradation of DSF. Finally, an optimum DSF‐LE was obtained with good stability after being accelerated at 60°C for 5 days and at 25°C for 3 months. Practical applications: DSF is extremely unstable in gastric juice and blood, so the currently available oral formulation of DSF has limited its clinical application. Here we propose a DSF‐LE to increase the therapeutic amount of drug reaching the cancer to improve its application in cancer treatment. In addition, some influences of formulation were investigated in detail. The investigation of pH control and properties of lecithins might have some guiding significances for industrial manufacture. In this article, a stable intravenous disulfiram‐loaded lipid emulsion was developed. The influences of pH values, oil, and lecithin on the stability of drug in emulsion were researched to obtain an optimum formulation. In the end, a probable interaction of DSF with lecithin was given according to a series of investigations of naturally‐extracted and synthetic lecithins.