Threo-DOPS Controlled Release Formulation for Steady Plasma Levels

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Solution Overview

Problem

Existing threo-3-(3,4-dihydroxyphenyl)serine formulations experience sharp peaks and troughs in blood plasma drug levels, leading to inadequate and unpredictable therapeutic effects for conditions associated with norepinephrine dysfunction, such as migraines and sympathetic nervous system disorders.

Innovation Solution

A controlled release pharmaceutical formulation combining an extended release component with an immediate release component, utilizing various delivery systems like dissolution-controlled, diffusion-controlled, and osmotic-controlled release systems, to maintain steady therapeutic concentrations of threo-DOPS in the blood plasma over an extended period.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional threo-DOPS formulations are used, then the drug is delivered to the patient, but sharp peaks and troughs in blood plasma drug levels occur resulting in unpredictable therapeutic effects

Engineering Contradiction:

Improvepredictability of therapeutic effectVSAvoidblood plasma drug level stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The formulation is segmented into two distinct components: an immediate release component containing threo-DOPS and an extended release component containing threo-DOPS. The immediate release component provides rapid initial drug delivery to achieve quick therapeutic effect, while the extended release component provides sustained drug release to maintain steady plasma levels. This segmentation resolves the contradiction by separating the functions of rapid onset and sustained stability into distinct formulation components.

Inventive Principle:

Principle #1Segmentation

2Stability of the object's composition

If extended release formulation is used, then steady therapeutic levels are maintained over prolonged time, but rapid initial therapeutic effect is not achieved

Engineering Contradiction:

Improveblood plasma drug level stabilityVSAvoidrate of therapeutic effect onset

Core Design Contradiction:

Stability of the object's compositionVSSpeed

Solution Approach 1:

The formulation merges two release mechanisms into a single dosage unit: an immediate release component for rapid drug delivery and an extended release component for sustained drug delivery. The immediate release component ensures rapid onset of therapeutic effect by quickly releasing threo-DOPS into the bloodstream, while the extended release component maintains steady plasma levels over prolonged time. This combination resolves the contradiction by integrating both rapid action and sustained stability in one formulation.

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If multiple dosing is used to maintain therapeutic levels, then drug coverage is improved, but patient compliance and treatment simplicity are reduced

Engineering Contradiction:

Improvetherapeutic coverageVSAvoiddosing regimen simplicity

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The extended release component is designed to release threo-DOPS continuously over an extended period (e.g., 12-24 hours), maintaining therapeutic plasma levels throughout the dosing interval. This continuous release action eliminates the need for multiple dosing administrations while ensuring reliable therapeutic coverage. The formulation achieves prolonged drug action from a single dose, resolving the contradiction between therapeutic coverage and dosing simplicity.

Inventive Principle:

Principle #20Continuity of useful action

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 controlled release formulation achieves prolonged therapeutic effects by regulating drug release, providing rapid initial effects followed by sustained levels, thereby improving treatment outcomes for norepinephrine-related disorders by maintaining steady nerve terminal norepinephrine levels and preventing recurrence of symptoms.

Implementation Method 1

Dissolution controlled release. Drug particles or granules that have a reasonable aqueous solubility, such as threo-DOPS, can be coated with, or embedded in, a slowly soluble material.

Methodology Applied

Scientific EffectDissolution-controlled release:

Implementation Method 2

Diffusion controlled release. Two main types of diffusion controlled systems are typically used: reservoir devices and matrix devices.

Methodology Applied

Scientific EffectDiffusion-controlled release: Diffusion

Implementation Method 3

Osmotically controlled release. In this type of delivery system, a core containing the drug and an appropriate amount of an osmotically active salt is surrounded by a semipermeable membrane

Methodology Applied

Scientific EffectOsmotic-controlled release: Osmosis

Data Source

PatentUS8158149B2Threo-DOPS controlled release formulation

Publication Date: 2012.04.17 CHELSEA THERAPEUTICS INC

AI summary

The present invention relates to pharmaceutical formulations for the controlled delivery of threo-3-(3,4-dihydroxyphenyl)serine (threo-DOPS) and derivatives of it. Such formulations can contain an extended or slow release component that maintains therapeutic concentration of threo-DOPS in the blood plasma over a prolonged time period. They can be further combined with an immediate release formulation to produce a product that, when administered to a patient in need thereof, results in substantially steady levels of active drug, eliminating the sharp peaks and troughs in blood plasma drug levels experienced with the existing threo-DOPS formulations.