Sublingual Glatiramer Acetate Formulation for MS

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Solution Overview

Problem

Current administration methods for Glatiramer acetate, such as subcutaneous injections, face challenges including first-pass metabolism in the liver, degradation in the gastrointestinal tract, and invasiveness, which can reduce efficacy and patient compliance, particularly for treating multiple sclerosis.

Innovation Solution

Development of novel sublingual tablet and capsule formulations using a water-soluble, non-gelling matrix for Glatiramer acetate, enabling immediate release and rapid absorption through the sublingual mucosa, bypassing liver metabolism and gastrointestinal degradation, thus providing an alternative to invasive injection routes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If subcutaneous injection is used for Glatiramer acetate administration, then the drug can be delivered directly into the subcutaneous tissue, but the method is invasive and reduces patient compliance

Engineering Contradiction:
Improvedrug delivery efficacyVSAvoidpatient compliance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the mechanical injection system with a chemical dissolution system. The sublingual tablet dissolves in saliva to release Glatiramer acetate, which then diffuses across the sublingual mucosa into the bloodstream, eliminating the need for needles and injection mechanics while maintaining effective drug delivery

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The sublingual mucosa serves as an intermediary transport pathway between the administered tablet and the systemic circulation. This natural membrane allows direct absorption of the drug into the bloodstream, bypassing the need for mechanical injection while ensuring reliable delivery through its vascular and lymphatic networks

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If oral administration is used for Glatiramer acetate, then the method is non-invasive and easy to administer, but the drug undergoes first-pass metabolism in the liver and degradation in the gastrointestinal tract

Engineering Contradiction:
Improveadministration convenienceVSAvoiddrug bioavailability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent transitions from the gastrointestinal tract route to the sublingual mucosal route, changing the dimensional pathway of drug absorption. This bypasses the digestive system and first-pass liver metabolism by utilizing the highly vascularized sublingual region as an alternative absorption dimension that delivers directly to systemic circulation

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The invention extracts Glatiramer acetate from the gastrointestinal absorption pathway and places it directly into the sublingual absorption pathway. This separation removes the drug from the harmful environment of stomach acid, bile, and digestive enzymes, as well as from first-pass liver metabolism, while maintaining non-invasive administration

Inventive Principle:
Principle #2Taking out (Extraction)

3Duration of action of moving object

If gel-forming matrix is used in sublingual formulation, then controlled release is achieved, but immediate release required for rapid therapeutic benefit is compromised

Engineering Contradiction:
Improvedrug release controlVSAvoidtherapeutic response speed
Core Design Contradiction:
Duration of action of moving objectVSSpeed

Solution Approach 1:

Instead of using a gel-forming matrix to control release, the patent inverts the approach by using a non-gelling, water-soluble matrix that immediately releases the drug upon contact with saliva. This inversion prioritizes rapid therapeutic response over controlled extended release, matching the urgent need for quick immunomodulatory effect in multiple sclerosis treatment

Inventive Principle:
Principle #13The other way round (Inversion)

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 sublingual formulations increase bioavailability and provide rapid therapeutic benefits, reducing the frequency of relapses in multiple sclerosis patients with improved patient compliance and quality of life by ensuring high (>60%) immediate release of Glatiramer acetate within 30 minutes, facilitating immune system activation.

Implementation Method 1

rapid absorption through the sublingual mucosa, bypassing liver metabolism and gastrointestinal degradation

Methodology Applied
Scientific EffectPassive diffusion: Diffusion

Implementation Method 2

water-soluble, non-gelling matrix for Glatiramer acetate, enabling immediate release

Methodology Applied
Scientific EffectDissolution: Solvation

Data Source

PatentEP3119413B1Sublingual delivery of glatiramer acetate
Publication Date: 2021.05.12 MAPI PHARMA LTD
  • EP3119413B1 patent drawingFigure 1
  • EP3119413B1 patent drawingFigure 2

AI summary

The present invention provides Glatiramer acetate compositions in a non-gelling matrix, formulated for sublingual delivery.