Liquid Nimodipine Composition for Stable High-Concentration Dosing
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Solution Overview
Problem
Existing liquid nimodipine formulations, such as NYMALIZE®, suffer from stability issues due to degradation under certain conditions, leading to the formation of impurities like nimodipine related compound A, and require cumbersome administration methods.
Innovation Solution
Development of novel liquid pharmaceutical compositions with improved stability, higher nimodipine concentrations, and reduced degradation, using solvents like ethanol, polyethylene glycol, and water, with specific ratios to minimize impurity formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If liquid nimodipine formulations are stored under elevated temperature and humidity conditions, then the nimodipine degrades forming impurities like nimodipine related compound A, but storage stability is required for practical use
Solution Approach 1:
The patent introduces an intermediary substance (hydroxypropyl cellulose or hydroxypropyl methyl cellulose) that mediates between the nimodipine and the degrading environment (elevated temperature and humidity). This excipient acts as a protective matrix that prevents direct degradation of nimodipine while maintaining the liquid formulation's stability during storage
Solution Approach 2:
The patent changes the chemical composition parameters of the liquid formulation by incorporating specific excipients (hydroxypropyl cellulose or hydroxypropyl methyl cellulose) in controlled amounts. This parameter change modifies the formulation's resistance to degradation under elevated temperature and humidity, thereby improving storage stability without compromising the therapeutic effect
2Ease of operation
If capsule extraction method is used to administer nimodipine to patients who cannot swallow capsules, then the administration is cumbersome and time-consuming, but it provides a way to deliver the medication
Solution Approach 1:
The patent extracts the nimodipine from the cumbersome capsule form and delivers it in a ready-to-use liquid formulation. This eliminates the need for practitioners to perform needle extraction procedures, allowing direct administration of the liquid medication through nasogastric tubes or other appropriate routes, thereby saving time and simplifying the administration process
Solution Approach 2:
The patent segments the medication delivery system into a pre-prepared liquid formulation that can be directly administered without requiring further manipulation. This segmentation separates the medication from the complex capsule extraction process, enabling simpler and faster administration while maintaining dosage accuracy
3Measurement precision
If needle extraction of nimodipine from capsules is performed, then administration errors can occur, but the capsule form allows for precise dosing
Solution Approach 1:
The patent employs disposable liquid formulation containers that are pre-filled with the exact dosage required. This eliminates the need for repeated needle extraction and measurement procedures that can lead to errors. Each disposable container ensures precise dosing through its pre-formulated content, while eliminating the operational complexities and error risks associated with manual extraction and measurement
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.