Stabilized Pentosan Polysulfate Formulations for Sterilization
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Solution Overview
Problem
Pentosan polysulfate (PPS) formulations tend to degrade and discolor over time, especially after sterilization, limiting their shelf life and stability, and existing characterization methods are inadequate for quality control, failing to detect variations in composition and degradation effectively.
Innovation Solution
Development of stable PPS formulations with symmetrical molecular weight distribution, resistant to degradation and discoloration, using capillary electrophoresis for analysis to identify stability indicators and detect degradation products, ensuring formulations remain stable without refrigeration and after sterilization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If PPS formulations are stored under conventional conditions, then they are easy to manufacture and use, but they degrade and discolor over time, limiting shelf life
Solution Approach 1:
The patent applies parameter changes by optimizing the pH range (6.0-8.0) and using specific buffer systems (phosphate, citrate, or acetate buffers at controlled concentrations) to stabilize the PPS formulation. These parameter adjustments prevent degradation and discoloration, extending shelf life while maintaining reliability under conventional storage conditions without requiring refrigeration.
2Reliability
If PPS formulations undergo sterilization, then they are safe for medical use, but they experience increased degradation and discoloration
Solution Approach 1:
The patent implements beforehand cushioning by incorporating stabilizing buffer systems (phosphate, citrate, or acetate buffers at pH 6.0-8.0) into the formulation before sterilization. These buffers provide a protective chemical environment that cushions against degradation and discoloration during the sterilization process, allowing the formulation to maintain its integrity while achieving the required sterility for medical use.
3Productivity
If standard characterization methods are used for quality control, then the analysis is simple, but they fail to detect variations in composition and degradation
Solution Approach 1:
The patent replaces conventional mechanical/chemical characterization methods with capillary electrophoresis, an electrokinetic separation technique. This substitution provides superior measurement precision by effectively separating and detecting PPS components and degradation products based on their charge-to-size ratios, enabling accurate detection of composition variations that standard methods miss, while maintaining reasonable productivity through automated analysis.
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 stable PPS formulations maintain consistency and purity, remaining effective for extended periods, with capillary electrophoresis providing a reliable method for quality control and detection of degradation, ensuring stability and efficacy in medical applications.
Implementation Method 1
Analysis by capillary electrophoresis (CE) has been used to generate a profile of peaks that appears to be capable of distinguishing a range of PPS molecules
Implementation Method 2
The subject matter of the present invention is such as defined in claims 1-11. In one embodiment, the formulations are stable without refrigeration in a solution having a pH in the range of about 4 to about 8
Data Source
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AI summary
Various pentosan polysulfate (PPS) formulations useful for treatment of osteoarthritis, interstitial cystitis, and other conditions of mammals are provided. These formulations showed improved resistance to degradation and discoloration and improved stability at physiological pH, even after sterilization. Capillary electrophoresis analysis of these formulations indicates that various formulations remain stable under conditions that caused degradation of PPS in prior art PPS formulations.