Nalbuphine Sustained Release Oral Formulation for Pruritus

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for prurigo nodularis, a condition characterized by intense itching, lack effective oral formulations that provide sustained relief, leading to frequent dosing and potential side effects due to peak drug concentrations.

Innovation Solution

Development of sustained release formulations of nalbuphine, a kappa-opioid receptor agonist, which are administered orally and designed to release the drug over an extended period, reducing frequency of dosing and peak concentrations, thereby providing longer-lasting anti-pruritic effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If conventional immediate-release formulations are used, then rapid onset of action is achieved, but frequent dosing is required and peak concentrations cause side effects

Engineering Contradiction:

Improveonset of actionVSAvoidduration of anti-pruritic effect

Core Design Contradiction:

SpeedVSDuration of action of moving object

Solution Approach 1:

The drug delivery system is segmented into multiple functional layers: an immediate-release layer containing nalbuphine base for rapid onset, and a sustained-release layer containing nalbuphine hydrochloride for extended duration. This segmentation allows both rapid onset and prolonged effect to coexist without requiring frequent dosing.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The formulation performs preliminary action by providing an immediate-release component that rapidly achieves therapeutic effect upon administration, while simultaneously initiating sustained-release that maintains therapeutic levels over extended periods, thereby eliminating the need for frequent redosing.

Inventive Principle:

Principle #10Preliminary action

2Reliability

If conventional immediate-release formulations are used, then rapid therapeutic effect is achieved, but dosing frequency increases and side effects worsen

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidside effects from peak concentrations

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The formulation segments nalbuphine into two forms: nalbuphine base in the immediate-release layer for rapid therapeutic effect, and nalbuphine hydrochloride in the sustained-release layer for steady-state maintenance. This segmentation ensures reliable therapeutic effectiveness while avoiding harmful peak concentrations that cause side effects.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The formulation changes the physical-chemical parameters of nalbuphine by using different salts (base form vs. hydrochloride salt) with different dissolution rates. This parameter change allows the same active ingredient to provide both rapid onset and sustained release, maintaining therapeutic effectiveness while minimizing side effects from peak concentrations.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If frequent dosing is administered, then therapeutic coverage is maintained, but patient compliance decreases and side effects increase

Engineering Contradiction:

Improvetherapeutic coverageVSAvoiddosing frequency

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The formulation achieves continuity of useful action by combining immediate-release and sustained-release mechanisms in a single dosage form. The immediate-release layer provides initial therapeutic coverage while the sustained-release layer continuously maintains therapeutic levels over 12-24 hours, eliminating the need for frequent dosing and improving patient compliance.

Inventive Principle:

Principle #20Continuity of useful action

4Duration of action of moving object

If sustained release formulations are developed, then dosing frequency is reduced and peak concentrations are minimized, but formulation complexity increases

Engineering Contradiction:

Improveduration of anti-pruritic effectVSAvoidformulation structure

Core Design Contradiction:

Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The formulation uses segmentation into distinct layers (immediate-release and sustained-release) to achieve extended duration of action. While this creates a multi-layer structure, each layer uses straightforward pharmaceutical components (nalbuphine base and hydrochloride salt respectively), balancing complexity with effectiveness.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The formulation employs composite materials by combining nalbuphine base and nalbuphine hydrochloride in a single dosage form. This composite approach allows the formulation to provide both immediate and sustained release properties, achieving extended duration of action while maintaining a unified dosage form that is manageable in complexity.

Inventive Principle:

Principle #40Composite materials

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 sustained release formulations of nalbuphine offer extended relief from pruritus symptoms for at least 8-12 hours, potentially reducing dosing frequency and minimizing side effects by maintaining therapeutic blood levels of nalbuphine over a longer duration.

Implementation Method 1

nalbuphine, a kappa-opioid receptor agonist

Methodology Applied

Scientific EffectOpioid receptor agonism:

Data Source

PatentEP2931279B1Methods for treating pruritus

Publication Date: 2024.03.20 TREVI THERAPEUTICS INC

Figure 1

AI summary

The present invention relates to methods for treating pruritus with anti-pruritic compositions.