Interferon Beta Stabilization via Cyclodextrin Inclusion Complexes
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Interferon-beta pharmaceutical compositions face instability issues due to denaturation, aggregation, and chemical degradation, leading to reduced efficacy and potential side effects, with existing stabilizers like cyclodextrins not adequately addressing these challenges for interferons.
Innovation Solution
A stabilized liquid pharmaceutical composition comprising interferon, a buffer, hydroxypropyl-beta-cyclodextrin, an isotonicity agent, and an antioxidant, specifically designed to enhance solubility and stability, avoiding the use of human serum albumin and incorporating a bacteriostatic agent for extended shelf-life and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If interferon-beta is formulated in liquid pharmaceutical composition, then it can be administered effectively, but it undergoes denaturation and aggregation leading to reduced stability
Solution Approach 1:
The patent introduces cyclodextrin as an intermediary substance that forms inclusion complexes with interferon-beta, protecting it from denaturation and aggregation. The cyclodextrin acts as a mediator between the interferon and the formulation environment, maintaining interferon activity while improving stability during storage and administration.
Solution Approach 2:
The patent modifies formulation parameters by adjusting pH, adding stabilizing agents, and optimizing concentration levels to prevent interferon degradation. By changing these parameters, the formulation maintains interferon activity while reducing denaturation and aggregation processes.
2Stability of the object's composition
If existing stabilizers like cyclodextrins are used, then some stability improvement is achieved, but they do not adequately address denaturation and aggregation challenges
Solution Approach 1:
The patent creates a composite formulation system combining cyclodextrin with other stabilizing agents, buffers, and excipients that work synergistically. This composite approach provides comprehensive protection against denaturation and aggregation while maintaining interferon activity, overcoming the limitations of using cyclodextrin alone.
3Stability of the object's composition
If human serum albumin is used as a stabilizer, then interferon stability improves, but it introduces potential side effects and contamination risks
Solution Approach 1:
The patent removes human serum albumin from the formulation while replacing it with alternative stabilizing agents such as cyclodextrin and other non-protein excipients. This extraction of the problematic component eliminates side effects and contamination risks associated with HSA, while maintaining interferon stability through the alternative stabilizing system.
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 maintains at least 60% of labeled interferon activity over 24 months, offering a stable and effective formulation for interferon-beta, suitable for multiple-dose use with improved stability and reduced side effects.
Implementation Method 1
a cyclodextrin, preferably hydroxypropyl-beta-cyclodextrin
Implementation Method 2
an antioxidant
Implementation Method 3
a buffer
Implementation Method 4
an isotonicity agent
Data Source
AI summary
Stabilized liquid pharmaceutical composition comprising an interferon (IFN) or an isoform, mutein, fused protein, functional derivative, active fraction or salt thereof, wherein said formulation is a solution that comprises a buffer, a cyclodextrin, an isotonicity agent and an anti-oxidant are described here. Preferably the interferon is interferon beta-1a and the cyclodextrin is HPBCD. These formulations are stable at room temperature, thus bringing the advantage of lower costs for formulation storage and increased safety for the patient with respect to possible “errors” during handling. As a matter of fact, having such formulations stable at room temperature reduces the risk of formation of degradation products potentially responsible for adverse events (e.g. immunogenicity).