GLP-1 Liquid Formulation Stability via Excipient Mediation
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Solution Overview
Problem
Native GLP-1 peptides have a short half-life due to rapid metabolic degradation by DPP-4, making stable liquid formulations challenging, especially for GLP-1 analogues like ROSE-010 that form noncovalent aggregates.
Innovation Solution
Development of stable liquid pharmaceutical formulations of GLP-1 or GLP-1 analogues, such as ROSE-010, in aqueous solutions with buffering agents and tonicity agents, which maintain stability under physical stress, freeze-thaw conditions, and long-term storage, suitable for injection in pre-filled syringes or containers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If GLP-1 analogues like ROSE-010 are formulated in liquid solutions, then they can be administered via injection, but they form noncovalent aggregates that reduce stability
Solution Approach 1:
The patent employs excipients as intermediary substances that mediate between the GLP-1 analogue and the aqueous environment. These excipients prevent aggregate formation by interacting with the peptide molecules, thereby maintaining peptide stability while allowing liquid formulation for injection.
Solution Approach 2:
The patent optimizes formulation parameters including pH, ionic strength, and excipient concentrations to prevent aggregation. By carefully controlling these parameters, the formulation maintains peptide stability in liquid state suitable for injection without forming noncovalent aggregates.
2Ease of operation
If GLP-1 peptides are stored in liquid form for extended periods, then convenient administration is achieved, but metabolic degradation by DPP-4 reduces effectiveness
Solution Approach 1:
The patent removes or neutralizes the harmful DPP-4 enzyme from the formulation environment through careful selection of buffer systems and excipients that inhibit DPP-4 activity, thereby preventing metabolic degradation while maintaining liquid formulation for convenient administration.
Solution Approach 2:
The formulation includes protective agents that preemptively prevent DPP-4-mediated degradation before it can occur during storage. This preliminary protection ensures peptide bioactivity is maintained throughout the shelf life of the liquid formulation.
3Adaptability or versatility
If GLP-1 formulations are subjected to freeze-thaw cycles, then storage flexibility is improved, but physical stress causes aggregation and loss of bioactivity
Solution Approach 1:
The patent incorporates protective excipients that cushion the peptide molecules against the physical stress of freeze-thaw cycles. These excipients form a protective environment around the peptides, preventing aggregation and maintaining bioactivity even after repeated freeze-thaw exposure.
Solution Approach 2:
The formulation uses a composite system combining multiple excipients with complementary protective functions. This composite approach provides multi-layered protection against freeze-thaw stress, maintaining peptide stability and bioactivity while enabling storage flexibility.
Data Source
AI summary
Stable liquid formulations of GLP-1 and GLP-1 analogues and method of using such formulations in the treatment of disorders or conditions are provided.