Lyophilized Protein Composition for Room-Temperature Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing lyophilized therapeutic protein formulations lack long-term stability at room temperature, leading to degradation issues such as aggregation and chemical modifications, which are not adequately addressed by current excipient compositions and processing methods.
Innovation Solution
A lyophilized therapeutic protein formulation with controlled residual moisture levels between 0.5% and 10% and specific excipient ratios, including buffers, stabilizers, and surfactants, is developed to maintain stability for at least 24 months at room temperature, using a process that includes controlled freeze-drying and annealing to achieve a low mobility solid state.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If lyophilized therapeutic protein formulations are stored at room temperature, then distribution and storage convenience is improved, but protein stability deteriorates leading to aggregation and degradation
Solution Approach 1:
The patent applies parameter changes by optimizing the residual moisture content to a specific range (0.5-10%) and controlling the glass transition temperature through plasticizer selection and concentration. These parameter adjustments enable the formulation to maintain protein stability at room temperature while preserving ease of storage and distribution.
Solution Approach 2:
The patent uses composite materials by combining the therapeutic protein with multiple excipients including sugars (sucrose, trehalose), sugar alcohols (sorbitol, glycerol), and amino acids (arginine, alanine) in specific ratios. This composite formulation creates a protective matrix that stabilizes the protein at room temperature while maintaining operational convenience.
2Reliability
If residual moisture content is increased to improve protein stability at room temperature, then protein degradation is reduced, but excessive moisture may promote aggregation and chemical modifications
Solution Approach 1:
The patent precisely controls the residual moisture content parameter within the range of 0.5-10%, which is sufficient to plasticize the matrix and reduce protein mobility for stability, but not excessive to promote aggregation or chemical modifications. This optimized parameter range resolves the contradiction between stability and harmful effects.
Solution Approach 2:
The patent creates local quality differences by distributing moisture non-uniformly within the lyophilized matrix, concentrating it in regions where it provides maximum plasticizing effect on the protein-excipient complex while avoiding regions where excess moisture could promote degradation reactions.
3Device complexity
If conventional excipient compositions are used in lyophilized formulations, then formulation simplicity is maintained, but long-term stability at room temperature is insufficient
Solution Approach 1:
The patent employs composite materials by formulating a multi-component excipient system comprising sugars, sugar alcohols, and amino acids in specific ratios. This composite approach provides synergistic stabilization effects that achieve long-term room temperature stability while maintaining reasonable formulation complexity through established excipient classes.
Solution Approach 2:
The patent applies universality by selecting excipients that perform multiple functions simultaneously: sugars and sugar alcohols act as both stabilizers and plasticizers, amino acids provide both structural support and moisture control, and the combination offers both physical stabilization and chemical protection against degradation.
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 formulation achieves less than 2% protein degradation after 24 months at 25°C, with improved stability against aggregation and chemical changes, as measured by size exclusion chromatography, while maintaining therapeutic activity.
Implementation Method 1
Lyophilization (freeze drying under controlled conditions) is commonly used for long-term storage of proteins
Implementation Method 2
using a process that includes controlled freeze-drying and annealing to achieve a low mobility solid state
Implementation Method 3
Plasticizers may also be included to decrease global relaxation time and in some cases may help to preserve the native structure of proteins
Data Source
AI summary
Stable lyophilized therapeutic protein compositions and their methods of manufacture are provided. Specifically, the use of water as a solid cake plasticizer and protein stabilizer is described. Also, the inclusion of a multicomponent stabilizer comprising a larger molecular entity and a smaller molecular entity is described. Also, the inclusion of post-drying annealing under certain conditions improves protein stability. Proteins are predicted to remain stable over 24 months at 25° C.