Ready-to-Use Cyclophosphamide Liquid Formulations for Stable Storage
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Solution Overview
Problem
Existing cyclophosphamide formulations require reconstitution with a diluent liquid, leading to decreased ease of administration and limited storage stability, with impurities forming over time.
Innovation Solution
Development of stable, ready-to-use liquid parenteral formulations of cyclophosphamide using specific solvents and antioxidants, maintaining impurity levels below 0.5% even under accelerated conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If lyophilized Cyclophosphamide formulations are used, then storage stability is improved, but ease of administration deteriorates due to required reconstitution
Solution Approach 1:
The invention changes the physical state parameter from solid lyophilized form to liquid solution form by using specific solvents (ethylene glycol, propylene glycol, polyethylene glycol) that maintain stability while eliminating reconstitution requirements. This parameter change resolves the contradiction by achieving both stability and ease of administration in a single liquid formulation.
2Ease of manufacture
If reconstitution with diluent liquid is required, then manufacturing simplicity is improved, but storage stability deteriorates with impurity formation over time
Solution Approach 1:
The invention introduces specific glycol solvents as intermediaries that prevent impurity formation during storage. These solvents act as mediators between the drug substance and the environment, maintaining stability without requiring reconstitution, thus resolving the contradiction between manufacturing simplicity and storage stability.
Solution Approach 2:
The invention creates a composite liquid formulation combining Cyclophosphamide with specific ratios of glycol solvents and antioxidants. This composite material achieves both ease of manufacture and long-term storage stability by integrating multiple components that work synergistically to prevent degradation.
3Ease of operation
If liquid formulations are prepared, then ease of administration is improved, but storage stability deteriorates with glassiness and stickiness
Solution Approach 1:
The invention changes the formulation parameters by using specific glycol-based solvents with appropriate viscosity and freezing point characteristics. These parameter changes prevent glassiness and stickiness while maintaining liquid state for easy administration, resolving the contradiction between ease of administration and storage stability.
Data Source
AI summary
The present invention relates to stable ready to use liquid formulations of Cyclophosphamide for parenteral use. The ready to use composition comprises Cyclophosphamide dissolved in a solvent system comprising a solvent, cosolvent(s) and antioxidant(s).