Thiotepa Injectable Formulation Stability via Solvent System
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Solution Overview
Problem
The commercial formulation of injectable thiotepa requires complex processes, is costly, and necessitates a reconstitution step, which can lead to instability and failure to provide a clear solution.
Innovation Solution
A stable, ready-to-use injectable thiotepa solution is developed, incorporating pharmaceutically acceptable solvents, co-solvents, and solubilizing agents, such as ethanol and propylene glycol, that maintains at least 90% purity after storage, eliminating the need for reconstitution and ensuring stability and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If thiotepa is supplied as a lyophilized powder requiring reconstitution, then storage stability is improved, but ease of operation deteriorates due to the additional reconstitution step
Solution Approach 1:
The patent changes the physical state parameter of thiotepa from lyophilized powder to ready-to-use liquid solution, and adjusts the solvent system parameters (using specific solvents and co-solvents in optimized ratios) to achieve both stability and ease of administration in a single formulation
2Reliability
If complex manufacturing processes are used to ensure stability, then reliability is improved, but device complexity worsens
Solution Approach 1:
The patent performs preliminary stabilization by formulating thiotepa with specific solvents and co-solvents in optimized ratios before storage, incorporating stabilizing agents in advance, and establishing proper pH and osmolarity conditions during manufacturing to ensure long-term stability without requiring complex storage or handling procedures
Solution Approach 2:
The patent creates a composite formulation system combining thiotepa with specific solvents (e.g., ethanol, polyethylene glycol), co-solvents, stabilizing agents, and pH adjusters in optimized ratios, where each component contributes to overall stability and reduces manufacturing complexity
3Ease of operation
If improper reconstitution is allowed, then ease of operation is improved, but reliability deteriorates due to failure to provide clear solution
Solution Approach 1:
The patent eliminates the reconstitution step entirely by providing a ready-to-use liquid formulation that is stable and clear upon administration, making the reconstitution process obsolete and ensuring reliable solution clarity without requiring precise reconstitution techniques
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 solution provides a stable, easy-to-administer thiotepa formulation that retains high purity over time, suitable for cancer treatment, without the need for reconstitution, enhancing manufacturing efficiency and patient safety.
Implementation Method 1
A stable, ready-to-use injectable thiotepa solution is developed, incorporating pharmaceutically acceptable solvents, co-solvents, and solubilizing agents, such as ethanol and propylene glycol
Data Source
AI summary
A stable, ready-to-use injectable solution including thiotepa and one or more pharmaceutically acceptable solvents, co-solvents, and/or solubilizing agents. Formulations retain at least 90% and as high as 99% of the purity of thiotepa as measured by HPLC after storage at 25° C./60% RH for a period of 7 days. Certain formulations retain at least 99% of the purity of thiotepa as measured by HPLC after storage for at least six months at 2-8° C.