T Haby | PubMed Health

PubMedDate not supplied

Aztreonam for injection (lyophilized): development of an automated solution batching process utilizing volumetric powder feeders.

As part of a commitment to fully automate the manufacture of a lyophilized dosage form of Azactam (Aztreonam for Injection), an automated solution batching procedure was developed. The lyophilization process requires solution batching of Aztreonam and L-arginine, the two constituents of the product. To avoid preblending of aztreonam and L-arginine prior to dissolution, a batching process was developed which makes use of two separate volumetric powder feeders. In conjunction with a feedback pH control system, these powder feeders provided for (a) a faster batching process, (b) a tight control of solution pH during batching, (c) a failsafe system to prevent operator error and equipment malfunction. Data are presented correlating bulk densities of various powders with feeder output along with solution pH profiles determined using the manual mode and the automated feedback pH control system.

Automation↗

PubMedDate not supplied

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

The interaction between different components used in the preparation of a new radiodiagnostic agent, BMS-181321, was overcome by its lyophilization as a bilayered product. BMS-181321 is composed of a nitroimidazole ligand BMS-181032, that is complexed with technetium-99m just before it is used in radionuclide imaging studies. Stannous chloride is required to reduce technetium from the +7 to the +5 oxidation state before it can be complexed by the ligand. Because BMS-181032 is unstable in the presence of stannous chloride (when mixed in the liquid or solid state), the two components must be contained in separate vials. A bilayered lyophile was manufactured, containing the ligand and stannous chloride in separate layers in a single vial. The bilayered product was manufactured by first filling a solution of the ligand into a vial and freezing the solution. A solution containing stannous chloride was then filled into the same vial on top of the frozen layer of ligand, and this second layer was also frozen. The two frozen layers were then lyophilized to a dry solid cake. The resulting bilayered product showed stability comparable to that seen when the ligand and the reducing agent were contained in separate vials. The separation provided by the layering was sufficient to prevent any significant interaction between the reducing agent and the ligand.

Chemistry, Pharmaceutical↗