Ivabradine Hydrochloride Matrix Tablets for Reduced Peak Fluctuations
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Solution Overview
Problem
Current Ivabradine hydrochloride formulations experience rapid plasma concentration fluctuations leading to adverse effects and poor medication compliance due to their immediate-release nature, and existing sustained-release formulations face challenges in industrial scalability, efficacy, and stability.
Innovation Solution
A sustained-release tablet comprising Ivabradine hydrochloride, a gel matrix of hydroxypropylmethyl cellulose with varying viscosities, a pore-forming agent like microcrystallone or lactose, and a lubricating agent, prepared via a direct powder compression method, ensuring a 24-hour sustained release without altering the salt form.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If immediate-release tablet formulation is used, then rapid plasma concentration peak is achieved, but adverse effects increase and medication compliance deteriorates
Solution Approach 1:
The patent divides the single immediate-release dose into multiple sustained-release doses over 24 hours, segmenting the drug release profile to maintain therapeutic levels while reducing peak concentration adverse effects
Solution Approach 2:
The sustained-release matrix is designed in advance to control drug release kinetics, preliminarily establishing a gradual release profile that prevents rapid concentration peaks before they occur in immediate-release formulations
2Stability of the object's composition
If sustained-release formulation is developed, then trough plasma concentration fluctuations are reduced, but manufacturing complexity increases
Solution Approach 1:
The patent modifies the physical and chemical parameters of the drug formulation by adjusting matrix material composition, pore-forming agent ratios, and processing conditions to achieve sustained release without excessive manufacturing complexity
Solution Approach 2:
The formulation combines multiple materials (hydroxypropylmethyl cellulose, pore-forming agents, lubricants) in specific ratios to create a composite sustained-release matrix that balances performance and manufacturability
3Duration of action of moving object
If high-molecular-weight polyoxyethylene is used as sustained-release material, then sustained release effect is achieved, but peak concentration is reduced too much leading to poor curative effect
Solution Approach 1:
The patent creates local variations in the formulation structure through pore-forming agents that generate localized channels for drug release, ensuring both sustained release duration and adequate peak concentration for therapeutic effect
Solution Approach 2:
The formulation incorporates porous pore-forming agents that create a controlled porous structure in the sustained-release matrix, allowing regulated drug diffusion that maintains both sustained release and therapeutic peak levels
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 formulation achieves a significant reduction in peak concentration by about 50% compared to immediate-release tablets, maintains pharmacological effectiveness, and is suitable for industrial production with improved stability and flowability, providing a once-daily dosing option.
Implementation Method 1
a gel matrix sustained-release material
Implementation Method 2
hydroxypropylmethyl cellulose which is selected from a mixture of two hydroxypropylmethyl celluloses with viscosity indication values of 100000 mPa·s and 5 mPa·s
Implementation Method 3
a pore-forming agent and a lubricating agent
Implementation Method 4
the releasing rate of the drug is adjusted by changing the proportions of the two polymers
Data Source
AI summary
The present disclosure discloses an Ivabradine hydrochloride sustained-release tablet and a preparation method thereof. The sustained-release tablet contains Ivabradine hydrochloride, a gel matrix sustained-release material, a pore-forming agent and a lubricating agent. The gel matrix sustained-release material is hydroxypropylmethyl cellulose. The pore-forming agent is selected from one or a mixture of microcrystalline cellulose and lactose. The lubricating agent is selected from one or a mixture of colloidal silica and magnesium stearate. The sustained-release tablet just needs to be orally administered once a day to reduce the peak-trough concentration fluctuations, thereby reducing the frequency of medication administration for patients and improve the medication compliance of the patients.