PEG-IFN-beta Liquid Formulation Stability
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Solution Overview
Problem
Current pharmaceutical formulations of pegylated interferon-beta (PEG-IFN-β) often require reconstitution and are not in a ready-to-use, stable liquid form, which can lead to instability and loss of activity during storage and administration.
Innovation Solution
A liquid pharmaceutical composition comprising pegylated interferon-beta (PEG-IFN-β), a polyol excipient, a surfactant (poloxamer 188), and a sodium acetate buffer at a pH of 4.2±0.2, which is stable and ready-to-use, minimizing the need for reconstitution and maintaining biological activity over time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If PEG-IFN-β is formulated as a liquid pharmaceutical composition, then ease of operation is improved (no reconstitution needed), but stability deteriorates (protein aggregation and oxidation during storage)
Solution Approach 1:
The patent introduces poloxamer 188 as a surfactant intermediary that prevents protein aggregation by adsorbing at the protein-solvent interface. The polyol excipient acts as a stabilizing mediator that forms a protective hydration shell around the PEG-IFN-β molecules, preventing oxidation and aggregation during liquid storage.
Solution Approach 2:
The patent optimizes specific parameters including pH (adjusted to 4.2±0.2 using sodium acetate buffer to minimize protein denaturation), temperature (storage at 2-8°C to reduce kinetic energy and aggregation), and concentrations of stabilizing agents (poloxamer 188 and polyol at specific ratios) to maintain protein stability in liquid form.
2Productivity
If PEG-IFN-β is stored as a concentrated liquid formulation, then productivity is improved (ready-to-use), but loss of substance increases (degradation over time)
Solution Approach 1:
The patent performs preliminary stabilization actions during formulation by pre-combining PEG-IFN-β with poloxamer 188 and polyol excipients in optimized ratios before storage. This preliminary protection prevents degradation during subsequent storage and handling, ensuring high activity retention when administered.
Solution Approach 2:
The patent converts the potentially harmful concentrated state into a beneficial formulation by adding specific stabilizing agents. The concentrated liquid formulation, which would normally accelerate degradation, is transformed into a stable product through the synergistic action of poloxamer 188 (preventing aggregation) and polyol (preventing oxidation), thereby maintaining high interferon activity.
3Stability of the object's composition
If PEG-IFN-β is formulated with multiple excipients and surfactants, then stability is improved, but device complexity increases
Solution Approach 1:
The patent applies different functional excipients at specific localized concentrations: poloxamer 188 at 0.05-2% w/v for surface stabilization, polyol at 0.1-10% w/v for bulk phase stabilization, and sodium acetate buffer for pH control. Each component performs its specific stabilizing function at its optimized concentration level.
Solution Approach 2:
The patent uses poloxamer 188 as a multi-functional surfactant that simultaneously prevents protein aggregation, improves solubility, and provides steric stabilization. The polyol excipient serves multiple roles including hydration shell formation, freezing point depression, and oxidation prevention, reducing the need for additional specialized additives.
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 provides a stable, ready-to-use solution that maintains interferon activity and reduces protein aggregation and oxidation, ensuring at least 70% retention of labeled activity over 12 to 24 months when stored at 2-8°C, with no significant decrease in PEG-IFN-β content up to 6 weeks at 25°C and 2 weeks at 40°C.
Implementation Method 1
a surfactant (poloxamer 188)
Implementation Method 2
a sodium acetate buffer at a pH of 4.2±0.2
Implementation Method 3
an excipient, a surfactant and a buffer wherein said excipient is a polyol
Data Source
Figure 1
AI summary
The invention relates to a liquid pharmaceutical composition comprising a pegylated IFN-ß (PEG- IFN-ß), an excipient, a surfactant and a buffer wherein said excipient is a polyol, wherein said surfactant is a non-ionic surfactant and wherein said buffer is a sodium acetate buffer.