Controlled-Release Levodopa Dosing for Stable Plasma Levels

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Solution Overview

Problem

Existing 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 current formulations failing to provide twice or thrice daily dosing with minimal 'peak-to-trough' fluctuations.

Innovation Solution

A dosing regimen involving controlled release oral compositions of levodopa, administered twice or thrice daily, comprising immediate and modified release components, such as beads or pellets coated with controlled release materials, to maintain steady plasma levels and reduce motor fluctuations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If levodopa is administered orally without controlled release, then immediate therapeutic effect is achieved, but plasma levels fluctuate rapidly causing motor fluctuations

Engineering Contradiction:

Improveonset of actionVSAvoidplasma concentration stability

Core Design Contradiction:

SpeedVSStability of the object's composition

Solution Approach 1:

The levodopa dosage is segmented into multiple release phases using different bead types (immediate release, sustained release, and extended release beads) within a single capsule, allowing simultaneous achievement of rapid onset and prolonged stable plasma levels

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The composition employs periodic release patterns through enteric coating that prevents premature release in the stomach, then enables sequential release in the intestine, creating controlled periodic delivery of levodopa to maintain stable plasma concentrations

Inventive Principle:

Principle #19Periodic action

2Speed

If levodopa is released quickly from the dosage form, then rapid absorption occurs, but the drug passes through the absorption window too quickly causing waste

Engineering Contradiction:

Improveabsorption speedVSAvoidduration of absorption

Core Design Contradiction:

SpeedVSDuration of action of moving object

Solution Approach 1:

Different bead types with varying release characteristics (immediate release, sustained release, extended release) are segmented within the composition to provide a spectrum of absorption rates, ensuring levodopa remains in the absorption window long enough for complete uptake

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Enteric coating is applied preliminarily to protect levodopa from stomach acid and prevent premature release, ensuring the drug is released only when it reaches the optimal absorption site in the intestine

Inventive Principle:

Principle #10Preliminary action

3Stability of the object's composition

If levodopa is administered multiple times daily, then steady plasma levels can be maintained, but patient compliance decreases

Engineering Contradiction:

Improveplasma concentration stabilityVSAvoiddosing frequency

Core Design Contradiction:

Stability of the object's compositionVSEase of operation

Solution Approach 1:

Multiple release mechanisms (immediate release, sustained release, and extended release components) are merged into a single oral composition, allowing the patient to take one capsule instead of multiple doses throughout the day while maintaining stable plasma levels

Inventive Principle:

Principle #5Merging (Combining)

4Stability of the object's composition

If controlled release materials are used, then plasma levels are stabilized, but the dosage form complexity increases

Engineering Contradiction:

Improveplasma concentration stabilityVSAvoiddosage form complexity

Core Design Contradiction:

Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The complex controlled release function is segmented into discrete bead types with different release characteristics, each performing a specific release function, while the overall composition maintains a simple capsule format for easy administration

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS12458616B2Levodopa dosing regimen

Publication Date: 2025.11.04 AMNEAL PHARMACEUTICALS LLC

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.