Enhanced formulation stabilization and improved lyophilization processes

A method for lyophilizing a liquid formulation, wherein the method comprises the following steps:

• a) providing a liquid formulation comprising a pharmaceutical substance and a stabilizing agent, wherein the liquid formulation comprises a specific ratio of the pharmaceutical substance to the stabilizing agent;
• b) initiating a freezing step in order to obtain a frozen liquid by:
• i) introducing the liquid formulation provided in step (a) into a freeze drying chamber of a freeze dryer;
• and
• ii) cooling the liquid formulation to a freezing temperature, wherein the cooling is performed at a defined cooling rate in order to obtain a frozen liquid;
• c) initiating a primary drying step of the frozen liquid obtained in step (b) in order to obtain a partly dried product by:
• i) reducing the pressure in the freeze drying chamber to a pressure below the vapor pressure of ice, and
• ii) increasing the shelf temperature;
• d) initiating a secondary drying step of the partly dried product obtained in step (c) comprising heating the partly dried product obtained in step (c) to a drying temperature wherein the heating is performed at a defined heating rate in order to obtain a lyophilized composition comprising the pharmaceutical substance and the stabilizing agent;
• and
• e) equilibrating the pressure in the freeze drying chamber to atmospheric pressure and removing the lyophilized composition comprising the pharmaceutical substance and the stabilizing agent obtained in step (d) from the freeze-drying chamber.