Effervescent Oral Opiate Dosage Forms for Reduced Dosing

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Solution Overview

Problem

Current opiate formulations, such as fentanyl, are expensive and pose risks due to dose-dependent respiratory depression and potential for drug dependence, necessitating a reduction in opiate dosage while maintaining effective pain management.

Innovation Solution

Development of orally disintegrable/dissolvable effervescent dosage forms containing a pH adjusting substance and effervescent couples, which allow for reduced opiate doses to achieve comparable bioavailability and pain relief through buccal, gingival, or sublingual administration, with a dwell time of 5-30 minutes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional opiate formulations are used, then effective pain management is achieved, but high opiate doses cause respiratory depression and drug dependence

Engineering Contradiction:
Improvepain management effectivenessVSAvoidrespiratory depression and drug dependence
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical and chemical parameters of the opiate formulation by creating an orally disintegrable effervescent dosage form with specific pH conditions. This transformation allows the same opiate to achieve better bioavailability and pain management at lower doses, thereby reducing harmful effects while maintaining therapeutic effectiveness

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces effervescent couples and pH adjusting substances as intermediaries that facilitate opiate dissolution and absorption in the oral cavity. These intermediaries enhance the bioavailability of the opiate, allowing reduced dosing while achieving equivalent pain relief, thus resolving the contradiction between effectiveness and harmful effects

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If traditional opiate formulations are used, then pain relief is provided, but costs are high due to expensive opiate dosing

Engineering Contradiction:
Improvepain relief effectivenessVSAvoidopiate dosage cost
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

By transforming the opiate into an orally disintegrable effervescent formulation with controlled pH, the patent achieves enhanced bioavailability that allows significant reduction in the quantity of expensive opiate required, thereby maintaining pain relief effectiveness while reducing treatment costs

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The effervescent formulation self-dissolves in the oral cavity without requiring water or other solvents, providing complete drug delivery through buccal, gingival, or sublingual absorption. This self-service mechanism ensures maximum utilization of the limited opiate dose, reducing waste and cost

Inventive Principle:
Principle #25Self-service

3Quantity of substance

If effervescent couples and pH adjusting substances are added to reduce opiate dose, then bioavailability improves, but dosage form complexity increases

Engineering Contradiction:
Improveopiate dose requiredVSAvoiddosage form composition
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent merges multiple functional components (opiate, effervescent couples, pH adjusting substances, disintegrants, and fillers) into a single integrated orally disintegrable dosage form. This combination allows the complex formulation to work synergistically, achieving reduced opiate dosing while maintaining manageable manufacturing and administration processes

Inventive Principle:
Principle #5Merging (Combining)

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 described dosage forms enable effective pain management with reduced opiate doses, minimizing side effects and costs, and achieving comparable or higher bioavailability compared to traditional formulations, while reducing the risk of respiratory depression and dependence.

Implementation Method 1

The orally disintegrable dosage form includes an effervescent couple and a pH adjusting substance. The effervescent couple generates effervescence that acts as a penetration enhancer for the opiate.

Methodology Applied
Scientific EffectEffervescence: Bubble

Implementation Method 2

The orally disintegrable dosage form includes an effervescent couple and a pH adjusting substance, which provides a pH difference or change in the microenvironment at the surface contact area of the oral mucosa and the dosage form.

Methodology Applied
Scientific EffectpH adjustment:

Implementation Method 3

The dosage form is designed for buccal, gingival, or sublingual administration routes, allowing transport of the opiate from the oral cavity to the blood stream across the oral mucosa.

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentUS7862833B2Effervescent oral opiate dosage forms and methods of administering opiates
Publication Date: 2011.01.04 CEPHALON INC

AI summary

Opiate containing dosage forms and methods using same are described. These dosage forms include substantially less opiates by weight than known oral formulations. These dosage forms are intended for oral administration across the oral mucosa.