Dual GLP-1/GLP-2 Parenteral Composition for Stability and Isotonicity
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Solution Overview
Problem
Formulating stable and isotonic pharmaceutical compositions for GLP-1/GLP-2 dual agonists is challenging due to chemical instability, self-association, and osmotic imbalances, which can lead to degradation and injection site discomfort.
Innovation Solution
A chemically stable parenteral pharmaceutical composition comprising GLP-1/GLP-2 dual agonists with specific buffer and tonicity agents, such as mannitol or sodium chloride, maintains isotonicity and pH between 7.0 and 8.2, enhancing stability and reducing injection site irritation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptide-based drugs are formulated for parenteral administration, then they can be delivered effectively, but they suffer from chemical instability and degradation
Solution Approach 1:
The patent optimizes formulation parameters including pH (adjusted to specific ranges using buffers), ionic strength, and excipient concentrations to minimize deamidation and oxidation rates, thereby extending shelf-life while maintaining chemical stability
Solution Approach 2:
Buffer systems and excipients are introduced as intermediary substances that control the chemical environment, preventing direct degradation reactions of the peptide through pH control and protection from reactive oxygen species
2Object-affected harmful factors
If tonicity agents are added to achieve isotonicity, then injection comfort is improved, but chemical stability may be affected
Solution Approach 1:
The patent carefully selects and optimizes the concentration of tonicity agents (such as sodium chloride or mannitol) to achieve isotonicity while monitoring and adjusting other formulation parameters to maintain chemical stability
Solution Approach 2:
Buffer systems serve as intermediaries that decouple the functions of tonicity adjustment and pH control, allowing tonicity agents to be added without compromising chemical stability through proper buffering capacity
3Productivity
If peptide concentration is increased to reduce dosing frequency, then treatment efficiency improves, but self-association and precipitation risks increase
Solution Approach 1:
Excipients and surfactants are introduced as intermediary substances that interact with peptide surfaces to prevent self-association and aggregation, enabling higher concentrations to be maintained in solution without precipitation
Solution Approach 2:
The patent optimizes ionic strength, pH, and the presence of specific excipients to alter the physical chemistry of the solution, reducing inter-peptide interactions that lead to aggregation and precipitation at high concentrations
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 composition achieves high chemical stability and isotonicity, ensuring prolonged shelf-life and comfort during administration by minimizing degradation and osmotic shock.
Implementation Method 1
For comfort during administration, many dosage forms must be 'isotonic' with body fluids at the site of injection, e.g. parenteral, ophthalmic and nasal solutions. Pain and irritation at the site of administration may occur if the formulation is either hypertonic or hypotonic. Further isotonic compositions prevent osmotic shock at the injection site.
Implementation Method 2
The greatest control over hydrolytic reactions, including deamidation, is exerted by stable and reliable pH and buffer systems. Tonicity is the 'effective osmolality' and is equal to the sum of the concentrations of the solutes, which have the capacity to exert an osmotic force across the membrane.
Data Source
AI summary
The present invention relates to pharmaceutical compositions suitable for parenteral administration in human subjects. In particular, the present invention relates to isotonic pharmaceutical compositions for parenteral administration.