Carboplatin Infusion Solution Stability With Oxygen and Sulfate Control
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Solution Overview
Problem
Carboplatin solutions are highly unstable and prone to decomposition, forming hazardous compounds and particulate matter, leading to stability issues and recalls due to their short shelf life and instability in reconstituted forms.
Innovation Solution
A parenteral dosage form containing an aqueous solution of carboplatin with specific concentrations of 1 to 2 mg/ml, stabilized by ammonium sulfate and controlled oxygen levels, ranging from 5 to 50 ppm, in flexible infusion containers, which are physically and chemically stable for up to two years at room temperature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If carboplatin is stored as a reconstituted aqueous solution, then it can be administered directly without further preparation, but the solution becomes unstable and decomposes within 8 hours forming poisonous compounds and particulate matter
Solution Approach 1:
The patent prepares carboplatin solutions in advance at optimized concentrations (0.5-2.0 mg/ml) with stabilizing agents (ammonium sulfate at 0.1-5.0 mg/ml) and controlled pH (4.0-6.0), then stores them in sterile containers with nitrogen atmosphere. This preliminary preparation eliminates the need for reconstitution at the point of administration while maintaining stability for extended periods (up to 2 years) through refrigerated storage.
2Productivity
If carboplatin solutions are stored at room temperature for extended periods, then accessibility and ease of use improve, but the solutions decompose and form black precipitates and harmful byproducts
Solution Approach 1:
The patent systematically optimizes multiple parameters including carboplatin concentration (0.5-2.0 mg/ml), stabilizer concentration (ammonium sulfate at 0.1-5.0 mg/ml), pH (4.0-6.0), and storage temperature (2-8°C). These parameter changes collectively extend shelf life from 8 hours to 2 years while preventing decomposition and harmful byproduct formation.
Solution Approach 2:
The patent stores carboplatin solutions in sterile containers filled with nitrogen gas to create an inert atmosphere that prevents oxidation and decomposition. This inert environment protection is crucial for maintaining solution stability during extended storage periods.
3Volume of stationary object
If commercial carboplatin solutions are prepared with higher concentrations to reduce storage volume, then storage efficiency improves, but stability decreases and particulate matter appears leading to recalls
Solution Approach 1:
The patent identifies an optimal concentration range (0.5-2.0 mg/ml) where carboplatin solutions maintain both stability and appropriate storage density. Concentrations within this range, combined with stabilizing agents and controlled pH, prevent precipitation and decomposition while achieving space-efficient storage without compromising reliability.
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 remains stable under extreme stress conditions and maintains low impurity levels, eliminating the need for reconstitution and ensuring safe, long-term storage and administration without precipitation or discoloration.
Implementation Method 1
The solution comprises 1 mg/ml of carboplatin, stabilizing amount of ammonium sulphate
Implementation Method 2
optionally, dissolved oxygen content is in the range of about 5 to 50 ppm
Implementation Method 3
carboplatin decomposes to form highly poisonous compounds like di-p.-hydroxo-bis (cis-diammineplatinum (II)), and tri-p-hydroxo-tris (cis-diammineplatinum (II)) which appear as black silver deposits
Data Source
AI summary
A parenteral dosage form having an infusion container filled with an aqueous solution in volumes ranging from 40 ml to 500 ml comprising 1 mg/ml to 2 mg/ml of carboplatin, wherein the solution contains known impurity of 1, 1-cyclobutanedicarboxylic acid in an amount of not more than 1.0% by weight of carboplatin and the solution remains physically stable when stored at room temperature.