Drug retention and stability of solid lipid nanoparticles containing azidothymidine palmitate after autoclaving, storage and lyophilization

Abstract

Solid lipid nanoparticles (SLNs) were prepared using trilaurine (TL) as the SLN core and phospholipid (PL) as coating. Neutral and negatively charged PLs werc used to produce neutral and negatively charged SLNs. An ester prodrug of 3′-azido-3′-deoxythymidine (Zidovudine®, AZT), AZT palmitate (AZT-P), was synthesized and incorporated in the SLNs. The stability of SLN formulations containing AZT-P was studied at different temperatures. Drug retention and mean particle diameter of SLNs were determined after autoclaving, during temperature stability testing, and after lyophilization (with or without cryoprotectivc sugars) and reconstitution. There were no significant changes in the mean diameter and the zeta potential (C) of SLNs after autoclaving (121 °C for 20min). The amount of incorporated AZT-P was, however, slightly reduced due to the formation of hydrosoluble AZT. Auto-claved SLNs were stable for a period of 10 weeks at 20 °C but an increase in particle size and loss of AZT-P were observed at 4 and 37 °C. Trehalose was an effective cryoprotectant for preventing SLN aggregation during lyophilization and subsequent reconstitution. Thermal gravimetric analysis showed that lyophilized preparations contained approximately 1% water. Using appropriate trehalose to lipid ratios, AZT-P retention in the SLNs was 100% after reconstitution. Our results demonstrate that SLNs containing AZT-P can be autoclaved, lyophilized and reconstituted without significant changes in SLN diameter and ç potential or in the quantity of incorporated prodrug.

Key Words:

• Solid lipid nanoparticles
• 3′-azido-3′-deoxythymidine
• thermal stress
• stability
• lyophilization
• thermal analysis
• AZT