Liquid FSH Formulation Stabilization with Preservatives
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Solution Overview
Problem
Current liquid formulations of recombinant human FSH face stability issues due to protein denaturation and aggregation, leading to loss of activity and potential allergic reactions, especially when stored for extended periods, and require reconstitution before use, which is inconvenient for patients.
Innovation Solution
A liquid pharmaceutical composition of recombinant human FSH stabilized with benzalkonium chloride and benzyl alcohol as preservatives, which maintains stability and activity for extended periods without cooling, allowing for direct injection without reconstitution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If FSH is formulated as a liquid preparation, then ease of operation and patient convenience are improved, but protein stability deteriorates due to denaturation and aggregation
Solution Approach 1:
The patent introduces preservatives (benzalkonium chloride and benzyl alcohol) as intermediary substances that mediate between the liquid formulation environment and the FSH protein. These preservatives actively prevent protein denaturation and aggregation, enabling the liquid formulation to maintain stability while providing ease of use without reconstitution.
Solution Approach 2:
The patent creates a composite pharmaceutical formulation by combining FSH with multiple excipients including preservatives (benzalkonium chloride, benzyl alcohol), buffers (phosphate), and stabilizers (mannitol, methionine). This composite material approach allows the liquid preparation to simultaneously achieve protein stability, microbial protection, and ease of administration.
2Duration of action of stationary object
If FSH is stored for extended periods, then duration of action is improved, but protein stability deteriorates leading to loss of activity
Solution Approach 1:
The patent applies beforehand cushioning by incorporating preservatives and stabilizers into the liquid formulation before storage. The preservatives (benzalkonium chloride and benzyl alcohol) are pre-introduced to cushion against microbial contamination and protein degradation during extended storage, enabling the formulation to maintain at least 80% FSH activity over 6 months at 2-8°C.
3Reliability
If preservatives are added to prevent bacterial growth, then reliability is improved, but protein stability deteriorates due to inactivation and aggregation
Solution Approach 1:
The patent merges multiple preservatives (benzalkonium chloride and benzyl alcohol) into a single formulation system that works synergistically. This combination provides effective microbial protection while the buffered environment (pH 6.5-7.5) and stabilizers (mannitol, methionine) collectively protect the FSH protein from preservative-induced inactivation and aggregation.
4Stability of the object's composition
If freeze-drying is used to improve stability, then protein stability is improved, but device complexity increases due to reconstitution requirement
Solution Approach 1:
The patent inverts the conventional approach by formulating FSH as a stable liquid preparation instead of freeze-drying it. This inversion eliminates the reconstitution step and associated complexity while maintaining protein stability through the use of preservatives and stabilizers in the liquid medium, allowing direct injection without solvents.
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 provides high protein stability and improved local tolerance, maintaining at least 80% FSH activity over 6 months at 2-8°C, preventing bacterial growth, and allowing for multi-dose use without significant degradation or aggregation.
Implementation Method 1
A liquid pharmaceutical composition of recombinant human FSH stabilized with benzalkonium chloride and benzyl alcohol as preservatives, which maintains stability and activity for extended periods without cooling
Implementation Method 2
The composition further comprises optionally one or more other pharmaceutically acceptable excipients. In one embodiment, the composition contains methionine as an antioxidant.
Implementation Method 3
Current liquid formulations of recombinant human FSH face stability issues due to protein denaturation and aggregation, leading to loss of activity
Data Source
AI summary
The present invention relates to a liquid pharmaceutical composition comprising a follicle stimulating hormone polypeptide and benzalkonium chloride and benzyl alcohol as preservatives. The composition further comprises optionally one or more other pharmaceutically acceptable excipients. In one embodiment, the composition contains methionine as an antioxidant. The composition shows a good storage stability and is especially useful for the prophylaxis and treatment of disorders and medical indications where follicle stimulating hormone preparations are considered as useful remedies.