Controlled-Release Levodopa Regimen for Stable Plasma Levels
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Solution Overview
Problem
Current oral levodopa dosage forms struggle with rapid metabolism, leading to unpredictable plasma levels and motor fluctuations in Parkinson's disease patients, making it difficult to achieve steady plasma concentrations and effective duration-of-effect, especially with existing extended release versions failing to provide twice or thrice daily dosing and minimal 'peak-to-trough' fluctuations.
Innovation Solution
A dosing regimen involving controlled release levodopa compositions administered twice or thrice daily, comprising immediate and modified release components, allowing for steady plasma levels and reduced motor fluctuations, with formulations such as multiparticulate dosage forms that include a core containing levodopa coated with controlled release materials, optionally with enteric polymers, to manage PD symptoms effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oral levodopa is administered to treat Parkinson's disease, then motor symptoms are improved, but plasma levels become unpredictable and motor fluctuations occur
Solution Approach 1:
The levodopa dosage form is segmented into multiple particles with different release characteristics (immediate release and controlled release components), allowing simultaneous provision of rapid initial absorption and sustained release to maintain stable plasma levels over extended periods
Solution Approach 2:
The invention changes the release rate parameter of levodopa by using controlled release materials and enteric coatings, transforming the rapid metabolism issue into a controlled release profile that maintains stable plasma concentrations
2Duration of action of moving object
If extended release levodopa formulations are used, then duration of effect is increased, but absorption issues prevent steady plasma concentrations
Solution Approach 1:
The dosage form combines immediate release and controlled release components in segmented particles, ensuring that levodopa is released and absorbed in the upper gastrointestinal tract before passing through, thereby achieving both extended duration and stable plasma levels
Solution Approach 2:
Enteric coating materials act as intermediaries that protect levodopa from premature release in the stomach and facilitate controlled release in the small intestine, the primary absorption site, thereby improving both duration and stability
3Reliability
If levodopa is released in the lower gastrointestinal tract, then absorption is reduced, but controlled release formulations cause delayed release
Solution Approach 1:
Different portions of the dosage form have different release properties (immediate release and controlled release components), ensuring that levodopa is released at the appropriate location (upper GI tract) for optimal absorption while providing extended duration through controlled release mechanisms
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 regimen provides stable plasma levodopa levels, reducing 'Off' time and increasing 'On' time, minimizing motor fluctuations, and maintaining therapeutic benefits throughout the day, even during sleep, with improved emotional well-being and reduced perceptual problems.
Implementation Method 1
controlled release pharmaceutical compositions of LD
Implementation Method 2
optionally with enteric polymers
Data Source
AI summary
The invention is a method for treating patients with Parkinson's disease by orally administering a controlled release levodopa formulation and the method provides an improvement of a patient's total post-dose “Off” time, total post dose “On” time and total post dose “Good On” time compared to post-dose of treatment regimens with oral immediate release levodopa tablets.