Lyophilized Drug Product Drying for Target Residual Moisture
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Solution Overview
Problem
Conventional lyophilization processes are inefficient in achieving stable lyophilized products for long-term storage, particularly at room temperature, due to high residual moisture content and potential product collapse during drying.
Innovation Solution
A novel lyophilization method that includes conducting secondary drying at controlled rates of desorption, maintaining shelf temperatures equal to or slightly higher/lower than primary drying temperatures, or omitting secondary drying altogether, to achieve target residual moisture levels of 3-5%, thereby stabilizing the lyophilized product for room temperature or refrigeration storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional secondary drying is conducted at high shelf temperature (≥25°C) to remove desorbed solvent molecules, then residual moisture content is reduced, but product collapse and degradation occur
Solution Approach 1:
The patent changes the shelf temperature parameter from conventional high temperature (≥25°C) to low temperature (≤0°C) during secondary drying, while extending the drying time. This parameter change allows achieving target residual moisture content (3-5%) without causing product collapse or degradation, thus resolving the contradiction between moisture removal and product stability
Solution Approach 2:
The patent dynamically adjusts the drying process by conducting secondary drying at low temperature for extended periods, allowing the system to gradually reach equilibrium moisture content without sudden thermal stress that would cause collapse. This dynamic approach maintains product integrity while achieving desired moisture levels
2Reliability
If lyophilization process is optimized to achieve low residual moisture content for room temperature storage stability, then storage stability is improved, but processing time increases
Solution Approach 1:
The patent performs preliminary freezing and primary drying to remove frozen solvent molecules before conducting secondary drying at low temperature. This preliminary action prepares the product matrix to facilitate controlled moisture removal during secondary drying, achieving target residual moisture content (3-5%) for room temperature stability without excessive processing time
Solution Approach 2:
The patent maintains continuous vacuum conditions throughout the entire lyophilization process including secondary drying, ensuring continuous sublimation and desorption of moisture. This continuous useful action efficiently removes moisture over extended periods at low temperature, achieving stable residual moisture content without interrupting the drying process
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method achieves stable lyophilized products with targeted residual moisture content, enhancing storage stability at room temperature and improving refrigeration storage conditions by maintaining product integrity and reducing moisture-related degradation.
Implementation Method 1
freezing the formulation
Implementation Method 2
conducting primary drying on the formulation to remove the frozen solvent molecule by sublimation
Implementation Method 3
conducting secondary drying on the formulation to remove the desorbed solvent molecules
Implementation Method 4
conducting secondary drying on the formulation to remove the desorbed solvent molecules
Data Source
AI summary
Lyophilization methods for preparing protein formulations for long-term storage at room temperature or improved stability at refrigeration storage are provided. Specifically, the present application provides lyophilization methods to obtain a target percentage of residual moisture of a lyophilized product, such as 3-5% residual moisture. The secondary drying of the lyophilization can be conducted under controlling rate of desorption under a temperature which is similar to the shelf temperature of the primary drying. Alternatively, the lyophilization can be conducted without a distinguished secondary drying step.