Glatiramer Acetate Formulation Reducing Injection Volume

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Solution Overview

Problem

Current treatments for relapsing-remitting multiple sclerosis (RRMS) using glatiramer acetate face challenges with injection-site reactions, poor solubility, and stability issues, which affect compliance and efficacy.

Innovation Solution

A method involving a subcutaneous injection of a 0.5ml aqueous pharmaceutical solution containing 20mg glatiramer acetate and 20mg mannitol, with a pH of 5.5 to 7.0, to reduce injection-site reactions and maintain therapeutic efficacy, potentially using an auto-injection device for ease of administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Volume of moving object

If the concentration of glatiramer acetate is increased to reduce injection volume, then the volume of injection is reduced, but the solubility and stability of the formulation deteriorate

Engineering Contradiction:
Improveinjection volumeVSAvoidformulation stability
Core Design Contradiction:
Volume of moving objectVSStability of the object's composition

Solution Approach 1:

The patent changes the pH parameter of the formulation to between 5.5 and 7.0, which is within the physiological range, to improve the solubility and stability of glatiramer acetate at high concentrations (20mg/0.5ml). This pH optimization allows the formulation to maintain stability while achieving reduced injection volume.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces mannitol as an intermediary substance in the formulation. Mannitol acts as a stabilizing agent and osmotic agent that facilitates the solubility and stability of glatiramer acetate at high concentrations, enabling the reduced volume formulation without compromising formulation integrity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Volume of moving object

If the concentration of glatiramer acetate is increased to reduce injection volume, then the injection volume is reduced, but injection-site reactions increase

Engineering Contradiction:
Improveinjection volumeVSAvoidinjection-site reactions
Core Design Contradiction:
Volume of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent optimizes the pH parameter to physiological range (5.5-7.0), which reduces irritation at the injection site. This pH adjustment allows high concentration formulation (20mg/0.5ml) to be administered with reduced injection-site reactions compared to conventional formulations.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Mannitol is introduced as an intermediary that modulates the interaction between the formulation and tissue. It acts as a tissue-compatible agent that reduces local irritation and injection-site reactions, enabling the administration of concentrated glatiramer acetate with improved tolerability.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Volume of moving object

If the concentration of glatiramer acetate is increased to reduce injection volume, then the injection volume is reduced, but patient compliance deteriorates

Engineering Contradiction:
Improveinjection volumeVSAvoidpatient compliance
Core Design Contradiction:
Volume of moving objectVSEase of operation

Solution Approach 1:

The pH is adjusted to physiological range (5.5-7.0), which significantly reduces injection pain and local reactions. This improvement in comfort directly enhances patient compliance, allowing patients to adhere to the treatment regimen despite the higher concentration formulation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent converts the potential harm of high concentration (which would normally cause more reactions) into a benefit by using pH optimization and mannitol. The reduced injection volume becomes advantageous rather than harmful, improving compliance through easier administration and reduced side effects.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentEP2275086B1Reduced volume formulation of glatiramer acetate and methods of administration
Publication Date: 2012.03.14 TEVA PHARMA IND LTD
  • EP2275086B1 patent drawingFigure 1
  • EP2275086B1 patent drawingFigure 2
  • EP2275086B1 patent drawingFigure 3

AI summary

A method for reducing frequency of relapses in a human patient afflicted with relapsing-remitting multiple sclerosis (RRMS) comprising administering to the patient 0.5ml of an aqueous pharmaceutical solution of 20mg glatiramer acetate and 20mg mannitol.