Solid Pharmaceutical Composition Stability via Acidic Additives

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Solution Overview

Problem

The challenge is to suppress the chemical decomposition of a specific compound represented by the general formula (1) during pharmaceutical composition formation, particularly during pressure forming processes like dry granulation, where the cyclopropylaminomethyl structure is prone to degradation, leading to the formation of a different compound.

Innovation Solution

A solid pharmaceutical composition is formulated containing the compound of formula (1) or its salt, a cellulosic excipient, and a predetermined acidic substance with a pH of 4.0 or lower, specifically using glutamic acid hydrochloride, tartaric acid, citric acid, malic acid, fumaric acid, monobasic sodium citrate, glutamic acid, aspartic acid, or alginic acid, which helps in suppressing the chemical decomposition through dry granulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If pressure forming (dry granulation) is used to form the pharmaceutical composition, then the composition can be manufactured with good flowability and compressibility, but the cyclopropylaminomethyl structure of the compound decomposes chemically

Engineering Contradiction:
Improvemanufacturability of pharmaceutical compositionVSAvoidchemical stability of compound (1)
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

An acidic substance with pH 4.0 or lower is introduced as an intermediary component in the pharmaceutical composition. This acidic substance acts as a protective mediator that suppresses the chemical decomposition of the cyclopropylaminomethyl structure during pressure forming, while not interfering with the manufacturing process. The acidic environment created by this intermediary prevents the harmful chemical reaction that would otherwise occur under compression.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If conventional stabilization methods (adding low-melting point oils, fats, or hydrophilic substances) are used, then the compound stability may be improved, but the formulation complexity and potential adverse effects increase

Engineering Contradiction:
Improvechemical stability of compound (1)VSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The invention changes the chemical parameter (pH) of the pharmaceutical composition by incorporating an acidic substance with pH 4.0 or lower. This parameter change creates a chemical environment that inherently suppresses decomposition of the compound, eliminating the need for complex physical barriers or multiple stabilizing agents. The pH modification provides a straightforward chemical solution rather than a complex physical formulation approach.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP2990038B1Solid pharmaceutical composition
Publication Date: 2019.11.20 KYORIN PHARMACEUTICAL CO LTD
  • EP2990038B1 patent drawingFigure 1~2
  • EP2990038B1 patent drawingFigure 3~4
  • EP2990038B1 patent drawingFigure 5~6

AI summary

[Problem] To provide a solid pharmaceutical composition which contains a compound represented by general formula (1) for a salts thereof and suppresses decomposition of said compound or salt thereof, any a production method or said solid pharmaceutical composition. [Solution] This solid pharmaceutical composition contains a compound represented by general formula (1) or a salt thereof, a cellulosic excipient, and an acidic substance oil pH 4.0 or less.