FGF-18 Freeze-Dried Formulation Stability
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Solution Overview
Problem
Current pharmaceutical formulations of Fibroblast Growth Factor 18 (FGF-18) face stability issues due to chemical or physical instabilities such as denaturation and aggregation, which affect their potency and shelf-life, particularly when stored at room temperature, making them unsuitable for long-term use in treating cartilage disorders like osteoarthritis.
Innovation Solution
A stable freeze-dried formulation of FGF-18 is developed, comprising a buffer, a poloxamer surfactant, and a sugar as stabilizing agents, specifically using phosphate buffer, poloxamer 188, and sucrose, which maintains the protein's biological activity for extended periods when stored at room temperature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If FGF-18 is formulated in conventional pharmaceutical compositions, then the protein can be administered for treating cartilage disorders, but the formulation loses stability and biological activity over time due to denaturation and aggregation
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by using freeze-drying technology to create a lyophilized cake structure, adjusting pH to specific ranges (6-8), and optimizing excipient concentrations to achieve long-term stability at room temperature
Solution Approach 2:
The patent introduces specific excipients as intermediaries including polysorbates (0.01-10 mg/vial), poloxamers (0.01-10 mg/vial), and sugars (1-100 mg/vial) that act as stabilizing agents to prevent protein denaturation and aggregation during storage
2Reliability
If excipients are added to stabilize FGF-18, then protein activity is maintained, but the formulation complexity increases
Solution Approach 1:
The patent combines multiple stabilizing excipients (polysorbates, poloxamers, and sugars) into a single formulation system that works synergistically to provide comprehensive protection against protein degradation while maintaining a manageable composition structure
3Ease of operation
If FGF-18 is stored at room temperature, then storage convenience is improved, but chemical and physical instabilities increase leading to loss of potency
Solution Approach 1:
The patent performs preliminary stabilization actions during formulation development by optimizing pH, adding stabilizing excipients, and creating a freeze-dried structure that pre-prevents denaturation and oxidation before storage, enabling room temperature stability
Solution Approach 2:
The freeze-dried formulation creates a protected environment that isolates the protein from oxidative and hydrolytic conditions, effectively providing an inert atmosphere that prevents chemical degradation during room temperature storage
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 retains at least 80% of FGF-18's biological activity for up to 24 months at room temperature, minimizing oxidation and protein aggregation, thus providing a stable and effective solution for treating cartilage disorders upon reconstitution.
Implementation Method 1
stable freeze-dried (or lyophilized) formulation containing FGF-18
Implementation Method 2
freeze-dried formulations of Fibroblast Growth Factor 18 (FGF-18) protein
Data Source
AI summary
The invention relates to the field of pharmaceutical formulations. More particularly it is directed to freeze-dried formulations of Fibroblast Growth Factor 18 (FGF-18) compound and to methods of producing such formulations. The freeze-dried formulations according to the invention are stable upon storage for an appropriate period of time. They can be used, after reconstitution, for the treatment of cartilage disorders such as osteoarthritis or cartilage injury.