Immunoglobulin Single Variable Domain Solid Formulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for preparing solid formulations of immunoglobulin single variable domains face challenges due to protein instability, particularly chemical and physical instability, especially when exposed to heat in a liquid state under shear stress, which can lead to denaturation and aggregation, compromising biological activity.
Innovation Solution
A method involving wet granulation or coating processes where a solid carrier is agitated with a liquid containing immunoglobulin single variable domains and heated to evaporate the liquid, with temperatures between 40°C and 80°C, allowing for the formation of stable solid formulations without significant loss of biological activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If heat is applied to evaporate liquid during solid formulation preparation, then productivity and manufacturing efficiency are improved, but protein stability deteriorates due to denaturation and aggregation
Solution Approach 1:
The patent applies parameter changes by controlling temperature within a specific range (40-80°C) and adjusting process parameters such as humidity (5-50% relative humidity) and processing time to prevent protein denaturation while maintaining manufacturing efficiency. This resolves the contradiction by finding optimal parameter values that satisfy both productivity and protein stability requirements.
Solution Approach 2:
The patent employs beforehand cushioning by adding stabilizers and protective agents to the liquid formulation before heat application. These additives create a protective environment that cushions the protein against thermal stress, allowing heat evaporation to proceed without causing denaturation or aggregation, thus maintaining both productivity and protein stability.
2Loss of energy
If the liquid is exposed to heat in a liquid state, then evaporation efficiency is improved, but physical instability increases leading to aggregation and denaturation
Solution Approach 1:
The patent utilizes phase transitions by controlling the transition from liquid to vapor phase during evaporation. By carefully managing temperature and humidity parameters, the process enables efficient evaporation while preventing the protein from experiencing conditions that lead to aggregation. The controlled phase transition occurs at temperatures below the protein's denaturation point, maintaining physical stability.
Solution Approach 2:
The patent introduces intermediary substances such as stabilizers and excipients that mediate between the heat energy and the protein molecules. These intermediaries absorb excess thermal energy and prevent direct thermal damage to the protein structure, enabling efficient evaporation while maintaining physical stability and preventing aggregation.
3Ease of manufacture
If shear stress is applied during agitation, then mixing efficiency is improved, but chemical instability increases causing bond cleavage and modification
Solution Approach 1:
The patent applies dynamics by using gentle agitation methods that provide sufficient mixing efficiency without creating excessive shear stress. The agitation is dynamically adjusted to match the sensitivity of the protein, using low-speed mixing or gentle circulation patterns that maintain homogeneity while preventing bond cleavage and chemical modification.
Solution Approach 2:
The patent employs disposable or easily replaceable mixing elements designed to minimize shear stress. These specialized mixing components are optimized to provide adequate mixing efficiency while having a limited service life, after which they are replaced to ensure consistent gentle mixing conditions that protect protein chemical stability.
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 enables the production of stable solid formulations with retained biological activity and physical integrity, suitable for pharmaceutical or diagnostic applications, by withstanding heat and shear stress, and maintaining antigen binding activity even after storage.
Implementation Method 1
the mixture of carrier and liquid is exposed to heat, e.g. a heated air stream, to evaporate the liquid
Data Source
AI summary
Methods for preparing solid formulations of immunoglobulin singie variable domains are provided. The methods are based on contacting solid carrier(s) with a liquid comprising the immunoglobulin singie variable domains, e.g. by spraying the liquid onto the solid carrier(s), to cause granulation or coating of the carrier(s). During contacting the carrier is agitated, e.g. in a fluid bed, and the mixture of carrier and liquid is exposed to heat, e.g. a heated air stream, to evaporate the liquid.