Ivabradine Sustained-Release Framework Using Polyoxyethylene
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Solution Overview
Problem
Rapid release preparations of ivabradine hydrochloride lead to peak-valley phenomena in blood medicine concentration, causing excessive heart rate decrease and side effects like bradycardia, and conventional sustained release methods fail to achieve superior therapeutic effects due to instability and complexity.
Innovation Solution
A sustained-release preparation of ivabradine using polyoxyethylene or polyvinyl acetate-polyvinylpyrrolidone polymers as framework materials, prepared by direct compression, which moderates blood concentration and improves therapeutic efficacy and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If rapid release preparations of ivabradine hydrochloride are used, then the drug is rapidly and almost completely absorbed with peak plasma level reached in about 1 hour, but the blood medicine concentration increases so fast that the heart rate decreases too fast causing excessive bradycardia and side effects
Solution Approach 1:
The patent segments the rapid absorption process into controlled, sustained release phases by using specific framework materials (polyoxyethylene or polyvinyl acetate-polyvinylpyrrolidone polymer) that control the release rate of ivabradine, preventing the sudden peak concentration that causes bradycardia and side effects
Solution Approach 2:
The patent changes the release rate parameter of ivabradine from rapid to sustained by selecting framework materials with specific molecular weights and proportions, thereby modifying the plasma concentration profile to avoid excessive heart rate decrease while maintaining therapeutic efficacy
2Stability of the object's composition
If conventional sustained release methods are used, then the peak-valley phenomenon is reduced, but the methods fail to achieve superior therapeutic effects due to instability and complexity
Solution Approach 1:
The patent achieves stable sustained release by precisely controlling parameters such as framework material molecular weight (900,000-7,000,000 Da for polyoxyethylene), framework material proportion (30-95%), and drug content (5-20mg per tablet), creating a simple yet effective formulation that is both stable and industrially scalable
Solution Approach 2:
The patent uses composite framework materials (polyoxyethylene or polyvinyl acetate-polyvinylpyrrolidone polymer) combined with ivabradine in specific ratios to create a sustained-release preparation that achieves both stability and simplicity, avoiding the complexity of conventional methods
3Quantity of substance
If rapid release preparations are used, then the maximum plasma concentration is 22ng/ml at steady state, but the peak-valley phenomenon causes frequent administration requirements reducing patient compliance
Solution Approach 1:
The patent achieves continuous drug release over an extended period (maintaining effective levels for longer than rapid release preparations) by using framework materials that control the gradual release of ivabradine, eliminating the peak-valley fluctuations that necessitate frequent dosing and thereby improving patient compliance
Data Source
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AI summary
Disclosed is a sustained-release preparation of ivabradine or pharmaceutically acceptable salts thereof. The preparation contains ivavradine or pharmaceutically acceptable salts thereof and a sustained-release framework material, wherein the sustained-release framework material is selected from polyoxyethylene, or a mixture of polyoxyethylene and polyvinyl acetate or polyvinyl pyrrolidone.