Phosphaplatin Liquid Formulations Stabilized by Alkaline Buffers
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Solution Overview
Problem
The development of stable ready-to-use liquid formulations of phosphaplatin compounds for cancer treatment is challenging due to their degradation in aqueous solutions, especially under acidic conditions, which complicates their preparation and storage.
Innovation Solution
The creation of liquid pharmaceutical compositions comprising a phosphaplatin compound in an aqueous buffer solution with a pH of 7 or above, using phosphate or bicarbonate salts to stabilize the compound, allowing for multi-year stability at ambient temperature and ease of administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If phosphaplatin compounds are formulated in aqueous solutions for parenteral administration, then ease of administration and manufacturing is improved, but stability of the compound deteriorates due to degradation especially under acidic conditions
Solution Approach 1:
The patent applies parameter changes by adjusting the pH of the aqueous buffer solution to be at or above 7 (physiological or slightly alkaline range). This pH adjustment prevents acid-catalyzed degradation of the phosphaplatin compound while maintaining solubility and stability. The specific parameter changed is pH, which directly addresses the contradiction between ease of administration (requiring aqueous formulation) and stability (compromised under acidic conditions).
Solution Approach 2:
The patent uses an aqueous buffer solution as an intermediary medium between the phosphaplatin compound and the degradation pathway. The buffer components (phosphate, carbonate, or bicarbonate salts) act as mediators that maintain physiological pH, thereby preventing direct acid-catalyzed degradation while still allowing the compound to be in solution form for easy administration. This intermediary buffer system resolves the contradiction by creating a stable environment that permits both aqueous formulation and compound stability.
2Ease of operation
If liquid formulations are prepared for immediate use, then ease of administration is improved, but storage stability deteriorates requiring refrigeration or freezing
Solution Approach 1:
The patent applies parameter changes by optimizing the pH to physiological or slightly alkaline range (≥7) and selecting specific buffer components that provide both solubility and long-term stability. This parameter optimization enables the formulation to remain stable at ambient temperature for extended periods (multi-year stability), eliminating the need for refrigeration or freezing while maintaining ease of administration in liquid form.
3Ease of operation
If pH is adjusted to physiological range (7.3-7.4) to avoid clinical challenges, then ease of administration is improved, but stability deteriorates due to degradation under acidic conditions
Solution Approach 1:
The patent applies parameter changes by adjusting the pH to be at or above 7, which includes but is not limited to the physiological range of 7.3-7.4. This pH adjustment is critical because it prevents acid-catalyzed degradation of the phosphaplatin compound. The buffer system maintains this pH range, thereby simultaneously achieving ease of administration (physiologically compatible pH) and stability (prevention of degradation).
Solution Approach 2:
The buffer solution acts as an intermediary that maintains the pH at physiological or slightly alkaline levels, preventing the compound from being exposed to acidic conditions that would cause degradation. The buffer components (phosphate, carbonate, or bicarbonate salts) mediate between the need for physiological pH (for ease of administration) and the need to prevent acid-catalyzed degradation (for stability).
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, ready-to-use liquid formulation of phosphaplatin compounds that maintains potency over extended periods at ambient temperature, facilitating their use in cancer treatment with improved manufacturing and storage conditions.
Implementation Method 1
an aqueous buffer solution having pH at or above 7, with a preferred pH range of 7-9. The buffer solution is an aqueous solution comprising a phosphate salt, a carbonate/bicarbonate salt, or a combination thereof
Data Source
AI summary
Pharmaceutical compositions of phosphaplatin compounds, in particular buffered stable liquid formulations of pyrodach-2 ready for use in the treatment of various cancers, and methods of preparation are disclosed.