Carbetocin Formulation pH Optimization for Room Temperature Stability

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Solution Overview

Problem

Current uterotonic drugs for preventing postpartum hemorrhage, such as oxytocin and Syntometrine, have limitations including short half-life, side effects, and contraindications, while carbetocin offers a long-acting solution but requires refrigeration, limiting its stability and usability in tropical regions.

Innovation Solution

A liquid pharmaceutical composition of carbetocin with a pH range of 5.4 to 5.65 and a concentration of 0.05 to 0.5 mg/mL, which is room temperature stable for up to two years, allowing for use in ambulances and tropical regions without refrigeration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If carbetocin is formulated for long-acting uterotonic effect, then duration of action is improved, but stability at room temperature deteriorates

Engineering Contradiction:
Improveduration of actionVSAvoidstability at room temperature
Core Design Contradiction:
Duration of action of moving objectVSStability of the object's composition

Solution Approach 1:

The patent changes the pH parameter of the formulation to a specific range (5.0-6.0, preferably 5.2-5.6) to achieve both long-acting effect and room temperature stability. This parameter optimization allows the carbetocin formulation to maintain stability without refrigeration while preserving its extended duration of action compared to conventional oxytocin formulations

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If carbetocin requires refrigeration for stability, then stability is improved, but ease of operation deteriorates

Engineering Contradiction:
ImprovestabilityVSAvoidease of operation
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

By optimizing the pH to 5.0-6.0 and selecting appropriate excipients, the formulation achieves stability at room temperature (25°C) for at least 24 months, eliminating the need for refrigeration. This parameter change transforms the storage requirements, making the drug easy to operate and distribute in resource-limited settings without cold chain infrastructure

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If carbetocin is used in tropical regions, then adaptability is improved, but stability deteriorates due to heat and humidity

Engineering Contradiction:
ImproveadaptabilityVSAvoidstability
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The formulation is specifically designed with pH 5.0-6.0 and stabilized with appropriate excipients to withstand tropical conditions (high temperature and humidity). Stability studies confirm the formulation maintains integrity under these challenging environmental conditions, enabling deployment in tropical and developing regions where refrigeration is unavailable

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP4374878B1Pharmaceutical composition comprising carbetocin
Publication Date: 2025.02.12 FERRING BV
  • EP4374878B1 patent drawingFigure 1
  • EP4374878B1 patent drawingFigure 1a
  • EP4374878B1 patent drawingFigure 2~3

AI summary

The present invention relates to pharmaceutical compositions having improved stability.