1,4-Dihydropyridine Compositions for Chelation-Based Oxidation Control
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Solution Overview
Problem
Calcium channel blockers, particularly 1,4-dihydropyridines, are susceptible to oxidation, forming pyridine analogues with lower calcium channel blocking activity and increased toxicological effects, leading to product recalls and decreased therapeutic efficacy.
Innovation Solution
The inclusion of a chelating agent in pharmaceutical compositions comprising 1,4-dihydropyridines stabilizes the compounds, reducing the formation of pyridine analogues and maintaining therapeutic effectiveness by forming stable, ready-to-use injectable formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If 1,4-dihydropyridine compounds are used as calcium channel blockers, then therapeutic efficacy is achieved, but oxidation occurs forming pyridine analogues with lower activity and increased toxicity
Solution Approach 1:
A chelating agent is introduced as an intermediary substance that binds to metal ions, preventing them from catalyzing the oxidation of the 1,4-dihydropyridine compound. This mediator approach directly addresses the oxidation problem while preserving the therapeutic efficacy of the DHP.
Solution Approach 2:
The invention creates a chemically inert environment by incorporating a chelating agent that sequesters metal ions, effectively removing the catalytic metals that would otherwise promote oxidation. This inerting approach protects the DHP compound from oxidation without affecting its biological activity.
2Stability of the object's composition
If chelating agent is added to stabilize the 1,4-dihydropyridine compound, then oxidation is prevented, but composition complexity increases
Solution Approach 1:
The invention optimizes the concentration parameter of the chelating agent to a specific range (0.01-10% w/v) where sufficient stabilization occurs without excessive complexity. This parameter optimization balances stability improvement with compositional simplicity.
3Ease of operation
If pharmaceutical compositions are made ready-to-use without dilution, then ease of operation is improved, but stability over time deteriorates
Solution Approach 1:
The chelating agent is pre-added to the formulation during manufacturing, creating a stable foundation before use. This preliminary stabilization allows the product to maintain its integrity and activity throughout storage and administration without requiring dilution or special handling.
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 compositions demonstrate improved stability and reduced impurities, ensuring prolonged efficacy and safety for treating cardiovascular disorders without the need for dilution before use.
Implementation Method 1
The inclusion of a chelating agent in pharmaceutical compositions comprising 1,4-dihydropyridines stabilizes the compounds, reducing the formation of pyridine analogues
Implementation Method 2
a class of calcium channel blockers, namely 1,4-dihydropyridines ('DHPs'), are susceptible to oxidation of the dihydropyridine ring to the pyridine ring
Data Source
AI summary
Provided herein are pharmaceutical compositions comprising a class of calcium channel blockers and at least one chelating agent. More specifically, the pharmaceutical compositions comprise at least one 1,4-dihydropyridine (DHP) compound and at least one chelating agent. The chelating agents used in this disclosure can decrease the degradation of the constituent DHPs of the DHP compositions. The DHP compositions can be used to treat cardiovascular disorders and are more stable for prolonged periods of time.