Lyophilized Polypeptide Formulations Using Volatile Additives
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Solution Overview
Problem
Lyophilized biological molecules have long reconstitution times, which hinder their administration, particularly for self-administration by patients, as current methods primarily focus on formulation of reconstitution buffers rather than incorporating volatile additives to reduce this time.
Innovation Solution
Incorporating a volatile additive, specifically t-butanol at 0.5% to 5% by volume, into the lyophilization formulation of polypeptides to expedite the reconstitution process when combined with a pharmaceutically acceptable dispersing agent.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If lyophilization is used to stabilize biological molecules, then shelf-life and storage stability are improved, but reconstitution time increases
Solution Approach 1:
The invention changes the chemical composition parameters of the lyophilized formulation by incorporating volatile additives (surfactants, chelating agents, or alcohols) at specific concentrations (e.g., 0.1-10% v/v). These parameter changes modify the physical properties of the reconstituted solution, enabling faster dissolution and dispersion of the biological molecule while maintaining the stability benefits of lyophilization.
Solution Approach 2:
The volatile additive acts as an intermediary substance that facilitates the reconstitution process. During lyophilization, the additive modifies the matrix structure to prevent tight packing and aggregation. Upon reconstitution, it mediates between the dry powder and water, accelerating wetting and dissolution without requiring complex mechanical agitation, thus reducing reconstitution time while preserving shelf-life.
2Stability of the object's composition
If conventional lyophilization formulation is used, then storage stability is achieved, but reconstitution speed is slow
Solution Approach 1:
The invention creates a composite lyophilized formulation by combining the biological molecule with volatile additives (such as surfactants, chelating agents, or alcohols) in specific ratios. This composite structure prevents aggregation and maintains stability during storage, while the volatile components facilitate rapid reconstitution by modifying the powder matrix structure and improving wetting characteristics.
Solution Approach 2:
By adjusting the concentration and type of volatile additive in the formulation (e.g., 0.1-10% v/v), the invention optimizes both storage stability and reconstitution speed. The parameter changes in chemical composition create a formulation that maintains molecular stability during storage but dissolves rapidly when reconstituted, resolving the contradiction between stability and speed.
3Volume of stationary object
If lyophilized biological molecules are reconstituted in storage containers, then storage space is reduced, but reconstitution time increases
Solution Approach 1:
The volatile additive modifies the physical parameters of the lyophilized cake structure, creating a more porous and less dense matrix that reconstitutes faster even in the same storage container volume. This allows the formulation to maintain space efficiency while achieving rapid reconstitution without requiring additional equipment or larger containers.
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
Significantly reduces the reconstitution time of lyophilized polypeptides, making them more suitable for rapid administration and improving safety and efficacy by ensuring complete reconstitution before use.
Implementation Method 1
Lyophilization is a process which removes solvent from a solution to form solid or powder which is stable and easier to store at elevated temperature than the liquid. Lyophilization, also known as freeze drying, involves freezing followed by sublimation.
Implementation Method 2
the present invention is directed to the addition of a volatile additive to the formulation of the buffer used for lyophilization of a biological molecule
Data Source
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AI summary
The invention is directed to a method for producing a polypeptide composition comprising: combining a polypeptide with a volatile additive to form a liquid mixture and lyophilizing the liquid mixture to obtain a lyophilized polypeptide composition.