Amino Acid Buffers Reduce Biopharmaceutical Aggregation
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Solution Overview
Problem
Current pharmaceutical formulations for biopharmaceutical drugs face issues such as aggregation, which reduces efficacy and increases immunogenicity, and some ingredients are questionable in terms of tolerability, necessitating the development of alternative formulations that minimize aggregation and improve stability and safety.
Innovation Solution
A pharmaceutical formulation comprising a biopharmaceutical drug with a mono- or dicarboxylic acid having a backbone of 2-6 C-atoms or its salt, which acts as a buffer, along with stabilizers and other components, is used to reduce aggregation and enhance stability, suitable for both aqueous and lyophilized forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional buffers (phosphate, citrate) are used in biopharmaceutical formulations, then pH stability is achieved, but drug aggregation increases
Solution Approach 1:
The patent changes the chemical parameters of the buffer system by using amino acid-based buffers (histidine, arginine, lysine, aspartic acid, glutamic acid) instead of conventional phosphate or citrate buffers. This parameter change in buffer composition resolves the contradiction by maintaining pH stability while reducing drug aggregation, as amino acid buffers interact differently with biopharmaceutical drugs compared to traditional buffers.
Solution Approach 2:
The patent employs amino acid buffers that can be easily metabolized and cleared by the body, replacing conventional buffers that may cause aggregation. These amino acid-based buffers serve their pH stabilization function effectively and are then naturally processed, avoiding long-term accumulation that could lead to aggregation issues.
2Duration of action of stationary object
If stabilizers and conventional formulation ingredients are added to maintain stability, then shelf life is extended, but tolerability concerns arise
Solution Approach 1:
The patent uses amino acid-based buffers that are naturally occurring and easily metabolized by the human body, replacing conventional stabilizers that may cause tolerability issues. These amino acid buffers provide necessary stabilization during storage and are then safely processed by the body, extending shelf life without compromising tolerability.
Solution Approach 2:
The patent changes the chemical composition parameters of the formulation by using amino acid derivatives and metabolites as buffers and stabilizers. This parameter change in formulation composition resolves the contradiction by providing adequate stability for extended shelf life while ensuring the ingredients are well-tolerated due to their natural occurrence and metabolic pathways.
3Stability of the object's composition
If higher buffer concentrations are used to maintain pH, then pH stability improves, but drug aggregation increases
Solution Approach 1:
The patent uses amino acid buffers that can be effectively utilized at lower concentrations compared to conventional buffers. These amino acid-based buffers provide sufficient pH stability at lower concentrations and are then naturally metabolized, avoiding the aggregation issues that arise with higher concentrations of traditional buffers.
Solution Approach 2:
The patent changes the concentration parameters of the buffer system by demonstrating that amino acid-based buffers achieve effective pH stability at lower concentrations than conventional buffers. This parameter change in concentration resolves the contradiction by providing adequate pH control without inducing drug aggregation.
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 significantly reduces protein aggregation, maintains stability, and improves tolerability, as demonstrated by reduced poly-dispersity index and average protein radius under stress conditions, extending the shelf life and ensuring therapeutic effectiveness.
Implementation Method 1
pharmaceutical formulations are comprising a biopharmaceutical drug, either a non-organic buffer, or salt thereof, like a phosphate buffer, or a tricarboxylic acid, or salt thereof, like citric acid/citrate
Implementation Method 2
stabilisers are frequently added, like for example a cryoprotective agent
Data Source
Figure 1a
Figure 1b
Figure 2a
AI summary
The present invention is related to a pharmaceutical formulation comprising a biopharmaceutical drug, said composition further comprising at least one mono- or dicarboxylic acid with a backbone of 2-6 C-Atoms, or at least one salt thereof.