Abstract
Teniposide-containing bile salt-egg PC mixed micelles and their liposomes formed from dilution were investigated and compared for (i) their teniposide contents as a function of bile salt species, drug dose, the egg PC/BS molar ratio, total lipid concentration, ionic strength and storage states (freeze-thawed and freeze-dried state, and the presence of light and oxygen) and (ii) their mean particle size, stored under different conditions. The physical stability of teniposide in micelles and their liposomes increased with increasing hydrophobicity of bile salt the order being deoxycholate > cholate > conjugated cholate at all temperatures (10°C, 23°C, and 45°C) studied. Teniposide-micelles were more stable at lower egg PC/BS molar ratios, while teniposide-liposomes were more stable at higher ratios. Teniposide stability slightly increased at higher total lipid concentration, indicating that bile salt-egg PC mixed micellar systems were in dynamic states. The presence of neither light nor oxygen significantly affected the stability of teniposide over the time and temperature range studied. However, the presence of salt in micellar and liposomal solutions greatly reduced teniposide loss by precipitation. Freezing or freeze-drying of teniposide-micelles induced neither micellar aggregation nor drug leakage. The stabilization may be due to the presence of detergent-like bile salts in the system.
- Received May 11, 1995.
- Accepted July 24, 1995.
- Copyright © Parenteral Drug Association. All rights reserved.
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