Development of a stable single-vial formulation for a new technetium complex using bilayer lyophilization

Area of Science:

• Radiochemistry
• Nuclear Medicine
• Pharmaceutical Sciences

Background:

• BMS-181321 is a novel radiodiagnostic agent utilizing a nitroimidazole ligand (BMS-181032) complexed with technetium-99m.
• Stannous chloride is essential for reducing technetium-99m to the appropriate oxidation state for complexation.
• The ligand BMS-181032 is unstable when mixed with stannous chloride, necessitating separate storage.

Purpose of the Study:

• To develop a stable formulation for the radiodiagnostic agent BMS-181321.
• To overcome the inherent instability between the nitroimidazole ligand and stannous chloride.
• To enable the preparation of BMS-181321 in a single vial for improved convenience.

Main Methods:

• A bilayered lyophilization process was employed.
• A solution of the ligand BMS-181032 was frozen in a vial.
• A solution of stannous chloride was added as a second layer and also frozen.
• The bilayered frozen product was lyophilized to create a stable solid cake.

Main Results:

• The bilayered lyophilization effectively separated the ligand and stannous chloride.
• The resulting product demonstrated stability comparable to separate vial storage.
• Significant interaction between the reducing agent and the ligand was prevented.

Conclusions:

• Bilayered lyophilization is a viable method for stabilizing radiodiagnostic agents with incompatible components.
• This technique enhances the shelf-life and ease of preparation for BMS-181321.
• The method ensures the integrity of the radiodiagnostic agent prior to radionuclide complexation.