Effervescent Fentanyl Dosage Form for Rapid Mucosal Absorption

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Solution Overview

Problem

Current fentanyl formulations for managing breakthrough cancer pain are expensive and require high doses, leading to increased risk of side effects and drug dependence, with existing technologies struggling to provide effective pain relief with reduced drug amounts.

Innovation Solution

Development of an orally disintegrable effervescent dosage form containing at least 45% less fentanyl than traditional lozenge or tablet formulations, utilizing an effervescent couple, pH adjusting substance, and disintegrants like sodium starch glycolate to enhance absorption and reduce dosage requirements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If traditional lozenge or tablet formulations are used, then effective pain relief can be achieved, but high doses of fentanyl are required leading to increased cost and side effects

Engineering Contradiction:
Improvefentanyl doseVSAvoidpain relief effectiveness
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the physical and chemical parameters of the dosage form by incorporating effervescent agents (sodium bicarbonate and citric acid) that react to produce carbon dioxide bubbles. This creates a foaming matrix that increases the surface area and contact time of fentanyl with the oral mucosa, enhancing absorption efficiency and allowing lower doses to achieve effective pain relief

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The effervescent reaction causes a phase transition from solid components to a foaming semi-solid matrix upon contact with saliva. This phase change creates numerous small bubbles that increase the surface area for drug absorption and facilitate faster onset of action while reducing the total fentanyl dose required

Inventive Principle:
Principle #36Phase transitions

2Reliability

If high doses of fentanyl are administered, then adequate analgesia is achieved, but the risk of respiratory depression and drug dependence increases

Engineering Contradiction:
Improveanalgesia adequacyVSAvoidrespiratory depression risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The effervescent formulation changes the dissolution rate and absorption kinetics of fentanyl by creating a foaming matrix. This results in faster onset of action and more efficient absorption, allowing adequate analgesia to be achieved with lower doses that carry reduced risk of respiratory depression and dependence

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The effervescent reaction products (carbon dioxide bubbles and alkaline environment) act as intermediaries that enhance fentanyl absorption across the oral mucosa. This intermediary mechanism improves bioavailability and reduces the required dose, thereby lowering the risk of harmful effects while maintaining adequate pain relief

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If conventional formulations are used, then pain management is provided, but the cost of medication is high

Engineering Contradiction:
Improvepain management effectivenessVSAvoidmedication cost
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

By changing the formulation parameters to include effervescent agents, the patent achieves more efficient drug delivery and absorption. This allows the same level of pain management effectiveness to be achieved with lower fentanyl doses, thereby reducing medication costs while maintaining therapeutic efficacy

Inventive Principle:
Principle #35Parameter changes

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 new dosage form achieves comparable or superior pain relief with significantly reduced fentanyl amounts, providing faster onset and increased bioavailability, while minimizing side effects and drug dependence, through efficient absorption across the oral mucosa.

Implementation Method 1

The orally disintegrable tablet is effervescent and includes at least one effervescent couple in an amount which is capable of producing effervescence in the presence of saliva

Methodology Applied
Scientific EffectEffervescence: Chemical Bonding

Implementation Method 2

at least one pH adjusting substance in an amount which is capable of producing a change in the localized pH in the microenvironment at the surface contact area of the oral mucosa and the dosage form

Methodology Applied
Scientific EffectpH adjustment: Chemical Bonding

Data Source

PatentUS7858121B2Effervescent oral fentanyl dosage form and methods of administering fentanyl
Publication Date: 2010.12.28 CEPHALON INC

AI summary

Fentanyl-containing dosage forms and methods using same are described. These dosage forms include substantially less fentanyl by weight than known oral formulation and have advantages in terms of reduced cost and reduced side effects. These dosage forms are intended for oral administration of fentanyl across the oral mucosa.