CX-8998 Oral Controlled-Release Formulation for Essential Tremor
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for essential tremor, such as propranolol, are inadequate, and there is a need for a more effective and sustained delivery of T-type calcium channel antagonists to manage tremor symptoms without adverse effects.
Innovation Solution
An oral dosage form of a T-type calcium channel antagonist, such as CX-8998, is formulated with a combination of immediate and controlled release components to maintain therapeutic plasma levels for 12-24 hours, reducing the frequency of dosing and minimizing adverse events.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for essential tremor (e.g., propranolol) are used, then tremor symptoms can be managed, but treatment effectiveness is inadequate and adverse effects occur
Solution Approach 1:
The patent applies parameter changes by modifying the pharmacokinetic parameters of the T-type calcium channel antagonist through controlled release formulation. This changes the plasma concentration profile from immediate peak-and-drop patterns to sustained therapeutic levels, improving treatment effectiveness while reducing adverse effects associated with peak concentrations
Solution Approach 2:
The dosage form is segmented into controlled release components that release the active ingredient at different rates. This segmentation allows the drug to be delivered in a controlled manner over extended periods, maintaining therapeutic efficacy while minimizing adverse effects through optimized plasma concentration profiles
2Reliability
If T-type calcium channel antagonists are administered to maintain therapeutic levels, then tremor management improves, but dosing frequency increases and adverse events occur
Solution Approach 1:
The controlled release formulation ensures continuous therapeutic action by maintaining plasma concentrations of the T-type calcium channel antagonist within the therapeutic range for extended periods (12-24 hours). This continuity eliminates gaps in tremor management and allows for reduced dosing frequency while maintaining effectiveness
Solution Approach 2:
The patent employs dynamic release profiles where the formulation adjusts drug release rates to maintain optimal plasma concentrations. The controlled release mechanism dynamically balances drug release to prevent both sub-therapeutic levels and toxic peaks, enabling less frequent dosing
3Speed
If immediate release formulations are used, then rapid onset of action is achieved, but plasma levels fluctuate and adverse events increase
Solution Approach 1:
The controlled release formulation implements periodic drug release patterns that maintain steady plasma concentrations. Instead of single immediate release events causing peaks and troughs, the formulation provides periodic release at controlled intervals, smoothing out plasma level fluctuations and reducing associated adverse events
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 provides sustained therapeutic benefits with reduced adverse events by maintaining plasma concentrations of CX-8998 within a therapeutically beneficial range for 12-24 hours, enhancing daytime efficacy and limiting nighttime disturbances.
Implementation Method 1
T-type calcium channels are members of a family of voltage-activated calcium channels... A unique and discriminating property of T-type calcium channels is their ability to activate upon small depolarizations of the membrane, at relatively low voltages, allowing a surge of calcium entry into excitable cells that leads to further membrane depolarization
Data Source
AI summary
This invention relates to methods and materials for treating mammals having, or at risk of developing, one or more movement disorders (e.g., essential tremor, epilepsy, and/or Parkinson's disease). For example, compositions including one or more T-type calcium channel antagonists (e.g., one or more Cav3 antagonists such as CX-8998) are provided, as well as methods for administering such compositions to a mammal having, or at risk of developing, one or more movement disorders (e.g., essential tremor, epilepsy, and/or Parkinson's disease) to treat the mammal.