Liquid Nimodipine Composition for Stable High-Concentration Dosing
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Solution Overview
Problem
Existing liquid nimodipine formulations, such as NYMALIZE®, suffer from instability under certain conditions, leading to degradation and the formation of impurities like nimodipine related compound A, and require higher doses due to lower concentrations.
Innovation Solution
Development of novel liquid compositions with higher nimodipine concentrations and improved stability, using solvents like ethanol, polyethylene glycol, and water, with specific ratios to minimize degradation and impurities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If existing liquid nimodipine formulations (e.g., NYMALIZE®) are used, then the formulation can be administered as a liquid solution, but the formulation degrades under elevated temperature and humidity conditions forming impurities
Solution Approach 1:
The patent changes the chemical composition parameters by incorporating specific stabilizing agents (cyclic phosphate compounds, vitamin E acetate, and specific pH buffers) into the liquid formulation. These parameter changes modify the chemical environment to prevent degradation pathways, thereby maintaining formulation stability while preserving liquid administration benefits.
Solution Approach 2:
The patent introduces intermediary substances (stabilizing agents) that mediate between the nimodipine and environmental factors. These intermediaries (cyclic phosphate compounds, vitamin E acetate) act as protective agents that intercept degradation pathways and prevent direct interaction between nimodipine and degrading conditions.
2Ease of manufacture
If existing liquid nimodipine formulations are used, then the formulation can be stored at room temperature, but higher doses are required due to lower concentrations
Solution Approach 1:
The patent increases the concentration parameter of nimodipine in the liquid formulation by optimizing the solvent system and removing unnecessary excipients. This parameter change allows the same volume to deliver a higher dose, reducing the total volume required while maintaining stability under room temperature storage conditions.
3Quantity of substance
If needle extraction method is used to administer capsule contents, then the full liquid dose can be delivered, but the process is cumbersome and time-consuming
Solution Approach 1:
The patent prepares the liquid nimodipine formulation in advance in a ready-to-administer form that does not require capsule opening or needle extraction. The formulation is pre-mixed and packaged in a manner that allows direct administration, eliminating the need for time-consuming preparation steps while ensuring the full liquid dose is delivered.
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 new compositions maintain stability under elevated temperatures and humidity, reducing impurity formation and allowing for lower daily intake volumes while effectively treating conditions like subarachnoid hemorrhage.
Implementation Method 1
The new compositions maintain stability under elevated temperatures and humidity, reducing impurity formation
Data Source
AI summary
Liquid compositions comprising nimodipine having improved nimodipine concentrations are provided herein. Methods of improving neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms with the liquid compositions of the present invention are also detailed herein.