Aqueous FSH Formulation Stabilization
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Solution Overview
Problem
Current formulations of human follicle stimulating hormone (FSH) require refrigeration to maintain stability, limiting their shelf-life and convenience for self-administration at ambient or body temperature.
Innovation Solution
A novel aqueous formulation of FSH stabilized with a buffer system containing stabilizers, non-ionic surfactants, antioxidants, and preservatives, including sodium chloride, trehalose, mannitol, polysorbate 20, L-methionine, and phenol, which maintains stability and activity at elevated temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If FSH is formulated in aqueous solution for ease of administration, then convenience is improved, but stability deteriorates due to dissociation and denaturation
Solution Approach 1:
The patent introduces multiple stabilizing agents as intermediaries between FSH and the aqueous environment. These include surfactants (polysorbate 20, poloxamer 188) that prevent surface adsorption, amino acids (glycine, L-arginine) that prevent dissociation, and antioxidants (methionine, ascorbic acid) that prevent oxidation. These mediators create a protective microenvironment that maintains FSH stability in aqueous solution without requiring refrigeration.
Solution Approach 2:
The formulation uses a composite system combining multiple excipients with specific functions: buffers (phosphate, citrate) for pH control, surfactants for surface protection, amino acids for dissociation prevention, antioxidants for oxidation prevention, and osmotic agents (mannitol, sucrose) for structural stabilization. This composite approach synergistically addresses multiple degradation pathways simultaneously, enabling stable aqueous formulation at ambient temperature.
2Duration of action of stationary object
If refrigeration is used to maintain FSH stability, then shelf-life is improved, but convenience deteriorates due to storage requirements
Solution Approach 1:
The formulation modifies the chemical parameters of the aqueous environment to enhance thermal stability. By adjusting pH to physiological range (6.5-7.5) using buffers, adding osmotic agents at specific concentrations (mannitol 1-5%, sucrose 2-10%), and incorporating stabilizing agents at optimized levels, the formulation achieves stability at ambient temperature (20-25°C) without refrigeration, eliminating storage constraints while maintaining shelf-life.
3Stability of the object's composition
If lyophilization is used to stabilize FSH, then stability is improved, but complexity deteriorates due to reconstitution requirement
Solution Approach 1:
Instead of removing water to stabilize FSH (lyophilization), the invention inverts the approach by maintaining FSH in aqueous solution and adding stabilizing agents that prevent degradation. This eliminates the need for freeze-drying and reconstitution steps, providing a ready-to-use liquid formulation that is as stable as or more stable than lyophilized products while being significantly easier to administer.
4Stability of the object's composition
If stabilizing agents are added to prevent dissociation, then stability is improved, but purity deteriorates due to potential contamination
Solution Approach 1:
The patent uses pharmacopeial-grade excipients that are approved for parenteral administration, ensuring they meet strict purity specifications. These include USP-grade polysorbate 20, poloxamer 188, glycine, L-arginine, methionine, ascorbic acid, phosphate buffers, and osmotic agents. These materials are used at low concentrations and are considered safe and pure for injection, minimizing contamination risks while effectively stabilizing FSH.
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 achieves less than 5% dissociation after two hours at 55°C and maintains stability for a prolonged period, ensuring a reasonable shelf-life without refrigeration, making it suitable for use at room or body temperature.
Implementation Method 1
stabilized in a buffer containing one or more stabilizer, a non-ionic surfactant, an anti-oxidant, inorganic salt
Implementation Method 2
a non-ionic surfactant
Implementation Method 3
an anti-oxidant
Implementation Method 4
inorganic salt
Data Source
Figure 1~2
Figure 3~4
Figure 5
AI summary
The present invention relates to an aqueous formulation of a follicle stimulating hormone (hFSH) which is stabilized to maintain the activity of hFSH for a prolonged period of time.