Amorphous Tapentadol Phosphate Stability

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Solution Overview

Problem

Tapentadol phosphate, a crucial analgesic, has a tendency to liquefy rapidly, making it unsuitable for pharmaceutical compositions and dosage forms, which is undesirable for workability and regulatory compliance.

Innovation Solution

The development of amorphous tapentadol phosphate, which can be processed and formulated into stable pharmaceutical compositions and dosage forms, characterized by the absence of long-range order and presence of short-range order, preventing liquefaction at room temperature.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If tapentadol phosphate is prepared using conventional methods, then it can be obtained as a solid, but it liquefies within a few seconds making it unsuitable for pharmaceutical compositions

Engineering Contradiction:
Improvestability of tapentadol phosphateVSAvoidworkability of tapentadol phosphate
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent applies parameter changes by modifying the physical state of tapentadol phosphate from crystalline to amorphous form. This fundamental parameter change in molecular arrangement prevents the liquefaction issue while maintaining stability, making it suitable for pharmaceutical compositions and dosage forms.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite material system by combining tapentadol phosphate with specific excipients and using particular processing methods (such as spray drying or freeze drying) to produce a stable amorphous solid dispersion. This composite approach prevents liquefaction while maintaining the active ingredient's efficacy.

Inventive Principle:
Principle #40Composite materials

2Reliability

If tapentadol phosphate is prepared as described in WO 2012/051246 A1, then it can be obtained as solid, but it liquefies rapidly which is highly undesirable for regulatory requirements

Engineering Contradiction:
Improvecompliance with regulatory requirementsVSAvoidphysical stability of tapentadol phosphate
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent fundamentally changes the physical parameter of tapentadol phosphate from crystalline to amorphous state. This parameter change eliminates the rapid liquefaction observed in conventional preparations, ensuring physical stability and compliance with regulatory requirements for pharmaceutical compositions.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention introduces intermediary substances (excipients) that stabilize the amorphous tapentadol phosphate and prevent liquefaction. These intermediaries act as matrices or carriers that maintain the physical stability of the active ingredient under various conditions.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP3819287B1Amorphous tapentadol phosphate
Publication Date: 2023.09.20 RATIOPHARM GMBH
  • EP3819287B1 patent drawingFigure 1
  • EP3819287B1 patent drawingFigure 2
  • EP3819287B1 patent drawingFigure 3

AI summary

The present invention relates to tapentadol phosphate in crystalline form and to a process for producing tapentadol phosphate in crystalline form. Further, the present invention relates to a composition comprising crystalline tapentadol phosphate and to a dosage form containing the composition of the invention.