Liquid Cetrorelix Stabilization with Poloxamer
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Solution Overview
Problem
Current Cetrorelix formulations are unstable and require reconstitution, limiting their shelf life and user convenience.
Innovation Solution
A liquid pharmaceutical composition comprising Cetrorelix or its pharmaceutically acceptable salt, a stabilizing agent such as poloxamer or benzyl alcohol, an osmotic agent like D-mannitol, and a pharmaceutically acceptable solvent containing an organic acid, which enhances stability and shelf life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If Cetrorelix is formulated as a liquid composition, then user convenience is improved by eliminating reconstitution, but stability deteriorates leading to short shelf life
Solution Approach 1:
Poloxamer 188 acts as a stabilizing intermediary substance in the liquid composition, preventing peptide aggregation and degradation. The poloxamer forms protective complexes with Cetrorelix, maintaining its stability in liquid form without requiring reconstitution, thus resolving the contradiction between ease of use and stability
Solution Approach 2:
The patent optimizes specific parameters including poloxamer concentration (0.1-10 mg/ml), pH (3.0-5.0), and ionic strength to achieve stable liquid formulations. By carefully controlling these parameters, the composition maintains both liquid state stability and peptide integrity, eliminating the need for reconstitution while preserving stability
2Stability of the object's composition
If Cetrorelix is provided as freeze-dried powder, then stability is improved, but device complexity increases due to reconstitution requirement
Solution Approach 1:
The patent extracts and eliminates the reconstitution step by incorporating stabilizing agents directly into the liquid formulation. This removes the need for separate lyophilized powder and reconstitution water components, simplifying the supply chain and reducing device complexity while maintaining stability through the poloxamer-based stabilization system
Solution Approach 2:
The patent merges the stabilizing agent, osmotic agent, and Cetrorelix into a single stable liquid composition that can be directly administered. This consolidation eliminates multiple components and steps, reducing supply chain complexity while maintaining stability through the synergistic combination of poloxamer 188 with osmotic agents like mannitol
3Duration of action of stationary object
If stabilizing agents are added to liquid Cetrorelix, then shelf life is prolonged, but manufacturing precision requirements increase
Solution Approach 1:
The patent establishes specific parameter ranges for poloxamer concentration (0.1-10 mg/ml), pH (3.0-5.0), and osmotic agent concentration that balance shelf life extension with manufacturing feasibility. These optimized parameters achieve prolonged stability without requiring excessive manufacturing precision, making the formulation practical for production
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 achieves high stability and prolonged shelf life, reducing the complexity of the supply chain and improving user convenience by eliminating the need for reconstitution.
Implementation Method 1
liquid Cetrorelix compositions can be stabilized by the incorporation of particular stabilizing agents
Implementation Method 2
an osmotic agent, preferably D-mannitol
Data Source
Figure 1a~1b
Figure 1c~1d
Figure 2a~2b
AI summary
The present invention refers to a liquid pharmaceutical Cetrorelix composition comprising a stabilizing agent selected from poloxamer having an t average molecular weight of 7,000-12,000 g/mol and/or benzyl alcohol, a pharmaceutical dosage form comprising said liquid pharmaceutical composition, and their use in inhibiting premature luteinizing hormone surges in woman undergoing controlled ovarian stimulation. Further, a method for preparing the liquid pharmaceutical Cetrorelix composition and pharmaceutical dosage form is disclosed.