Pridopidine Modified Release Formulation for Cmax Reduction

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Solution Overview

Problem

Current pridopidine formulations result in high maximum plasma concentrations (Cmax) that can lead to adverse events such as QT interval prolongation, gastrointestinal disorders, and psychiatric issues, necessitating a modified release form that reduces Cmax while maintaining therapeutic efficacy.

Innovation Solution

A modified release solid oral dosage form of pridopidine incorporating pharmaceutically acceptable rate controlling excipients, such as polymeric materials like hydroxypropyl methylcellulose and hydrogenated castor oil, to control the release of pridopidine, thereby reducing peak plasma concentrations and extending the duration of drug action.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If immediate release formulations are used, then rapid drug absorption occurs, but maximum plasma concentrations become excessively high causing adverse events

Engineering Contradiction:

Improveabsorption rateVSAvoidadverse events from high Cmax

Core Design Contradiction:

SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent applies dynamics by transitioning from static immediate release to dynamic modified release formulations that adapt drug release rates. Multiple formulation types (sustained-release, controlled-release, extended-release) provide different release kinetics, allowing optimization between absorption speed and peak concentration control for different clinical scenarios

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent employs parameter changes by modifying physical and chemical properties of the drug delivery system. Factors such as polymer composition, particle size, coating thickness, and formulation matrix are adjusted to control release kinetics, thereby managing Cmax while maintaining therapeutic efficacy

Inventive Principle:

Principle #35Parameter changes

2Power

If immediate release formulations are used, then quick therapeutic effect is achieved, but duration of action is insufficient requiring frequent dosing

Engineering Contradiction:

Improvetherapeutic effect intensityVSAvoidduration of drug action

Core Design Contradiction:

PowerVSDuration of action of moving object

Solution Approach 1:

The patent implements continuity of useful action through modified release formulations that provide sustained drug delivery over extended periods. The formulations maintain therapeutic plasma concentrations continuously, eliminating the peaks and valleys associated with immediate release dosing and enabling once-daily or less frequent administration

Inventive Principle:

Principle #20Continuity of useful action

Solution Approach 2:

The patent applies periodic action through formulations designed with specific release patterns that deliver drug at optimized intervals. The periodic release profiles are engineered to maintain therapeutic levels throughout the dosing interval, providing consistent efficacy without accumulation

Inventive Principle:

Principle #19Periodic action

3Quantity of substance

If high doses are administered to maintain therapeutic levels, then efficacy is improved, but maximum plasma concentrations increase causing toxicity

Engineering Contradiction:

Improvedrug dosageVSAvoidtoxicity from high Cmax

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent applies segmentation by dividing the total daily dose into multiple smaller releases throughout the dosing interval. The modified release formulations segment the drug delivery process, releasing small amounts continuously rather than all at once, thereby maintaining efficacy while preventing toxic peak concentrations

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses intermediary materials such as polymer matrices, coating layers, and release-modifying excipients that mediate between the drug and the body. These intermediaries control the release rate, allowing high total doses to be delivered safely by preventing direct rapid absorption into systemic circulation

Inventive Principle:

Principle #24Intermediary (Mediator)

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 modified release form achieves a safer pharmacokinetic profile by lowering Cmax and maintaining or exceeding the area under the curve (AUC) compared to immediate release forms, reducing adverse events while providing sustained therapeutic effects.

Implementation Method 1

A modified release solid oral dosage form comprising a therapeutically effective amount of Pridopidine or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable rate controlling excipient

Methodology Applied

Scientific EffectDrug release control:

Data Source

PatentUS20240041855A1Modified release formulations of pridopidine

Publication Date: 2024.02.08 PRILENIA NEUROTHERAPEUTICS LTD

AI summary

The subject invention provides a modified release solid oral dosage form comprising a therapeutically effective amount of Pridopidine or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable rate controlling excipient, wherein the solid oral dosage form provides an in vivo plasma pridopidine concentration profile having a Mean Cmax of about 1,400 ng/ml or less. The subject invention also provides a method of treating an individual afflicted with a neurodegenerative disease or disease related to dopamine, comprising once daily administration of a modified release solid oral dosage form.