Enteric Muco-Adhesive Levodopa Formulation for Steady Plasma Levels
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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 extended absorption and steady plasma levels of levodopa, including immediate and sustained release mechanisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If oral delivery of levodopa is used, then ease of administration is improved, but plasma concentration control deteriorates due to peak-to-trough fluctuations
Solution Approach 1:
The levodopa dosage is divided into multiple particles with different release characteristics. Some particles provide immediate release while others provide sustained release, creating a segmented delivery system that maintains steady plasma levels without the peak-to-trough fluctuations of conventional single-dose formulations.
Solution Approach 2:
The invention changes the release rate parameter of levodopa by using particles with different coating properties. Fast-release particles have permeable coatings allowing rapid dissolution, while slow-release particles have less permeable coatings that control the release rate, thereby achieving stable plasma concentration profiles.
2Ease of operation
If conventional oral levodopa formulations are used, then ease of administration is improved, but duration of effect deteriorates due to short duration-of-effect
Solution Approach 1:
The formulation segments levodopa delivery into immediate-release and sustained-release components. The sustained-release particles extend the duration of effect by providing prolonged levodopa release, thereby addressing the short duration-of-effect limitation of conventional formulations while maintaining oral administration convenience.
Solution Approach 2:
The invention ensures continuous therapeutic action by combining fast-release particles that provide initial levodopa levels with slow-release particles that maintain levels over an extended period. This continuous release profile prevents the rapid decline in plasma concentration seen with conventional formulations.
3Stability of the object's composition
If intestinal infusion of levodopa is used, then plasma concentration stability is improved, but device complexity and invasiveness worsen
Solution Approach 1:
The invention makes the levodopa particles self-regulating through their inherent coating properties. The particles automatically release levodopa at controlled rates based on their permeability characteristics without requiring external control mechanisms, pumps, or complex delivery systems, thereby achieving plasma stability through self-service release kinetics.
Solution Approach 2:
The coating materials on the levodopa particles serve as intermediaries that control release kinetics. These coatings act as rate-limiting barriers that modulate levodopa release without requiring complex external control systems, simplifying the overall delivery mechanism while maintaining plasma concentration stability.
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 prolonged therapeutic coverage with minimal fluctuations, rapid 'on' effect, and sustained plasma levels of levodopa, addressing motor fluctuations in Parkinson's disease patients.
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) a plurality of controlled release components comprising (i) a core comprising a mixture of levodopa and at least one pharmaceutically acceptable excipient, (ii) a controlled release coating surrounding the core, (iii) a muco-adhesive coating surrounding the controlled release coating and (iv) an enteric coating surrounding the muco-adhesive coating; and (b) one or more immediate release components comprising levodopa.