Muco-Adhesive Controlled-Release Levodopa for Rapid Onset
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Solution Overview
Problem
Existing oral levodopa formulations for Parkinson's disease fail to provide steady plasma concentrations, leading to 'peak-to-trough' fluctuations and short duration-of-effect, necessitating improved oral delivery systems for sustained therapeutic levels.
Innovation Solution
A controlled release oral dosage form comprising a muco-adhesive and enteric-coated components, with a rate-controlling material, to achieve prolonged and steady drug absorption, including immediate and sustained release components for levodopa and optional decarboxylase inhibitors like carbidopa.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If oral levodopa formulations are used, then rapid onset of action is achieved, but plasma concentration fluctuations and short duration-of-effect occur
Solution Approach 1:
The oral dosage form is divided into multiple distinct components: an immediate release component containing levodopa and carbidopa for rapid onset, and a controlled release component with mucoadhesive and enteric coatings for sustained release. This segmentation allows each component to perform its specific function - the immediate release portion provides quick therapeutic effect while the controlled release portion maintains steady plasma levels over extended periods
Solution Approach 2:
The formulation employs periodic release patterns through the controlled release component, which releases levodopa in a sustained manner over time. The mucoadhesive coating provides initial retention followed by controlled dissolution, creating a periodic action pattern that extends duration-of-effect while maintaining therapeutic levels
2Ease of operation
If oral levodopa formulations are used, then ease of administration is improved, but plasma concentration control deteriorates
Solution Approach 1:
The oral formulation is segmented into immediate release and controlled release components, each with specific coating characteristics. The immediate release component provides rapid absorption for quick therapeutic effect, while the controlled release component with mucoadhesive and enteric coatings ensures sustained release and stable plasma concentrations, thereby achieving both ease of administration and plasma concentration control
Solution Approach 2:
The formulation utilizes parameter changes in the coating materials - the mucoadhesive coating changes from adherent to dissolving state, and the enteric coating dissolves at specific pH levels. These parameter changes enable controlled release kinetics that maintain stable plasma concentrations while preserving the ease of oral administration
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 rapid 'on' effect with sustained therapeutic plasma levels of levodopa, minimizing fluctuations and extending the duration of action beyond existing oral dosage forms.
Implementation Method 1
formulated with a muco-adhesive material and an enteric material
Implementation Method 2
formulated with a muco-adhesive material and an enteric material
Implementation Method 3
with a rate-controlling material, to yield enhanced drug delivery attributes
Data Source
AI summary
The invention provides an oral solid formulation comprising (a) one or more controlled release components comprising a core comprising levodopa, esters or salts thereof and wherein the one or more controlled release components; and (b) one or more immediate release components comprising levodopa, esters or salts thereof. The oral solid formulation also contains a decarboxylase inhibitor and about 80% to 100% of the decarboxylase inhibitor present in the oral solid formulation is present in the one or more immediate release components.