Stabilization and preformulation of anticancer drug--SarCNU

Area of Science:

• Pharmaceutical Chemistry
• Drug Stability Studies
• Analytical Chemistry

Background:

• SarCNU (1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea) is a nitrosourea compound with potential therapeutic applications.
• Understanding its stability in various pharmaceutical formulations is crucial for effective drug delivery and storage.

Purpose of the Study:

• To investigate the degradation kinetics and stability profile of SarCNU in different pharmaceutically acceptable solvents.
• To determine the influence of various environmental factors and excipients on SarCNU stability.

Main Methods:

• High-performance liquid chromatography (HPLC) was employed to quantify SarCNU degradation.
• Stability was assessed across a range of solvents (water, ethanol, DMSO, etc.), temperatures, pH conditions, and in the presence of common excipients.
• Degradation kinetics were analyzed, including order of reaction and half-life determination.

Main Results:

• SarCNU degradation follows first-order kinetics and is catalyzed by both general and specific acids and bases.
• Factors such as light, ionic strength, antioxidants (ascorbic acid, sodium bisulfite), and EDTA did not significantly affect degradation rates.
• Stability was markedly higher (25-50 times longer t(90)) in pure cosolvents like ethanol compared to aqueous or semi-aqueous vehicles.

Conclusions:

• SarCNU stability is primarily governed by pH-dependent acid-base catalysis, with oxidation not being a significant degradation pathway.
• Nonaqueous ethanol serves as a suitable solvent for long-term storage of SarCNU as a concentrate.
• Dilution with aqueous solvents prior to administration is recommended for SarCNU formulations.