Nefopam Controlled Release Formulation for ADHD Treatment

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Solution Overview

Problem

Conventional nefopam preparations have a short elimination half-life, leading to difficulty in maintaining analgesic efficacy and an increased frequency of adverse drug reactions due to plasma peak concentrations, especially when administered parenterally, and existing treatments for conditions like ADHD and anxiety disorders have side effects.

Innovation Solution

The use of nefopam, particularly its (+) enantiomer, in controlled release formulations to extend therapeutic effects and reduce side effects, including combination with other drugs like psycho-stimulants or monoamine reuptake inhibitors, for treating affective disorders such as ADHD, anxiety disorders, and eating disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional release preparations of nefopam are administered three times daily, then analgesic efficacy can be maintained, but the frequency of adverse drug reactions increases due to plasma peak concentrations

Engineering Contradiction:
Improveanalgesic efficacyVSAvoidadverse drug reactions
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies periodic action by using controlled release technology to deliver nefopam at regulated intervals, transforming the dosing pattern from three times daily to once or twice daily while maintaining therapeutic levels and reducing peak concentration-related adverse effects

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent changes the release rate parameter of nefopam from immediate release to controlled release, thereby altering the plasma concentration profile to reduce peak levels while maintaining adequate therapeutic levels over extended periods

Inventive Principle:
Principle #35Parameter changes

2Reliability

If dose escalation of nefopam is performed to maintain analgesic efficacy, then pain relief is improved, but the frequency of adverse drug reactions increases

Engineering Contradiction:
Improveanalgesic efficacyVSAvoidadverse drug reactions
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the release kinetics parameter from immediate to controlled release, allowing lower total doses to achieve the same therapeutic effect while reducing adverse reactions, thereby resolving the need for dose escalation

Inventive Principle:
Principle #35Parameter changes

3Speed

If parenteral delivery of therapeutic doses of nefopam is used for rapid pain relief, then analgesic onset is improved, but adverse effects on pulse and blood pressure occur

Engineering Contradiction:
Improveanalgesic onsetVSAvoidadverse effects on pulse and blood pressure
Core Design Contradiction:
SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent uses controlled release to create a gradual, periodic delivery of nefopam, avoiding the sudden plasma spike from parenteral delivery while maintaining adequate analgesic onset through optimized release kinetics

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The controlled release formulation acts as an intermediary between immediate parenteral delivery and oral administration, providing a controlled transition that achieves rapid enough onset while filtering out the harmful peak concentration effects

Inventive Principle:
Principle #24Intermediary (Mediator)

4Reliability

If existing treatments for ADHD and anxiety disorders are used, then therapeutic effects are achieved, but side effects occur

Engineering Contradiction:
Improvetherapeutic effectVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the pharmacokinetic parameters of nefopam through controlled release formulation, creating a smoother concentration-time profile that reduces side effects while maintaining therapeutic efficacy for ADHD and anxiety disorders

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent combines nefopam with controlled release delivery systems and potentially other drugs (as mentioned in the summary), creating a composite therapeutic approach that enhances efficacy while reducing side effects

Inventive Principle:
Principle #40Composite materials

Data Source

PatentEP1993533A2Use of nefopam for the treatment of affective disorders
Publication Date: 2008.11.26 SOSEI R&D LIMITED

AI summary

Nefopam is used for the manufacture of a medicament for the treatment of an affective disorder such as ADD or ADHD.