Freeze-Drying Biologically Active Proteins with Non-Polymeric Sugars
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for preserving biologically active proteins through freeze-drying face challenges with long drying times due to the use of non-polymeric sugars, which lead to structural damage and loss of biological activity, while polymeric sugars offer higher glass transition temperatures but inferior stabilization properties.
Innovation Solution
A method involving freeze-drying of biologically active proteins in a protective matrix with high concentrations of non-polymeric sugars, where the frozen bodies are supported in a way that at most 30% of their surface is contiguous with restraining elements, allowing for shorter drying times without significant loss of activity, using a combination of conduction and radiation heat transfer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-polymeric sugars are used as protective agents in freeze-drying, then protein stabilization is improved, but drying time increases exponentially
Solution Approach 1:
The invention changes the physical parameters of the freeze-drying process by controlling temperature profiles and pressure conditions to enable efficient sublimation of ice crystals formed during freezing, thereby reducing drying time while maintaining the protein-stabilizing benefits of non-polymeric sugars
Solution Approach 2:
The invention applies preliminary freezing of the aqueous composition before the drying phase, which transforms the liquid water into ice crystals that can then be rapidly removed through sublimation, significantly reducing the overall drying time compared to direct drying of liquid formulations
2Productivity
If drying temperature is increased to reduce drying time, then productivity is improved, but protein biological activity is lost
Solution Approach 1:
The invention utilizes the phase transition of water from solid (ice) to gas (vapor) through sublimation, allowing ice crystals to be removed directly without passing through the liquid phase, thereby enabling faster drying at lower temperatures that preserve protein biological activity
Solution Approach 2:
The invention employs periodic cycling between freezing and drying phases, where the composition is frozen to form ice crystals, then dried through sublimation, and potentially re-frozen if needed, creating a rhythmic process that optimizes both drying speed and protein preservation
3Reliability
If high amounts of non-polymeric sugar are used, then protein protection is improved, but matrix density increases causing exponential drying time increase
Solution Approach 1:
The invention changes the physical state parameters of the sugar-protein mixture by controlling the freezing process to create a specific ice crystal structure and distribution, which facilitates faster sublimation even in the presence of high sugar concentrations that would otherwise create dense matrices
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
This approach enables the production of a stable, homogenous freeze-dried product with high sugar content, achieving drying times under 48 hours while maintaining protein stability and activity, suitable for a broad spectrum of applications without the need for grinding or re-working.
Implementation Method 1
using a combination of conduction and radiation heat transfer
Implementation Method 2
using a combination of conduction and radiation heat transfer
Implementation Method 3
reducing the pressure in the drying apparatus below atmospheric pressure, and providing heat to the body (typically via conduction and/or radiation) in order to sublimate the frozen solvent of the body
Implementation Method 4
A method involving freeze-drying of biologically active proteins in a protective matrix with high concentrations of non-polymeric sugars
Implementation Method 5
lyophilisation (freeze-drying) processes, wherein aqueous compositions, usually comprising water as the main solvent, are frozen and then dried by sublimation
Data Source
AI summary
The present invention pertains to a method for producing a medicinal product comprising a biologically active protein comprising the steps of providing an aqueous composition comprising a solvent, the biologically active protein and between 20% w/w and 60% w/w of a non-polymeric sugar, freezing the composition, thereby forming at least one frozen body comprising the solvent in frozen form, putting the frozen body in a drying apparatus while being carried by a support, the support comprising one or more restraining elements that define one or more boundaries of the support, wherein at most 30% of the surface of the body is contiguous with the one or more restraining elements, reducing the pressure in the drying apparatus below atmospheric pressure, providing heat to the body in order to sublimate the frozen solvent of the body and obtain a dried body. The invention also pertains to a product obtainable by this method.