Linaprazan Glurate HCl Polymorphs for Solubility, Stability
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Solution Overview
Problem
Existing crystalline forms of linaprazan glurate have low solubility, high hygroscopicity, and chemical instability, limiting their effectiveness in pharmaceutical formulations for treating gastrointestinal inflammatory diseases.
Innovation Solution
Development of stable crystalline polymorphs of the hydrochloride salt of linaprazan glurate, specifically Forms 1 and 2, which exhibit higher solubility, lower hygroscopicity, and improved chemical stability, achieved through various crystallization techniques.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If crystalline forms of linaprazan glurate are used, then chemical stability is improved, but solubility deteriorates
Solution Approach 1:
The patent applies parameter changes by modifying the crystalline structure parameters of linaprazan glurate to create new polymorphs (Form 1 and Form 2) with different molecular arrangements. This changes the physical and chemical properties of the crystal lattice, resulting in improved solubility while maintaining chemical stability. The specific parameter changes include alterations in intermolecular distances, packing density, and hydrogen bonding patterns within the crystal structure.
Solution Approach 2:
The patent utilizes phase transitions by transforming linaprazan glurate from one crystalline phase to another through controlled crystallization processes. Different polymorphic forms represent different solid phases of the same compound, each with distinct solubility characteristics. By inducing specific phase transitions during crystallization, the patent achieves forms that balance both stability and solubility requirements.
2Quantity of substance
If amorphous materials are used, then solubility is improved, but chemical stability deteriorates
Solution Approach 1:
The patent applies parameter changes by transitioning from the amorphous state to ordered crystalline states, fundamentally changing the molecular arrangement parameters. This transformation maintains high solubility by preserving the bioavailability advantages of amorphous materials while introducing the chemical stability of crystalline structures through defined molecular packing and intermolecular interactions.
3Stability of the object's composition
If highly crystalline forms are used, then chemical stability is improved, but hygroscopicity deteriorates
Solution Approach 1:
The patent applies parameter changes by modifying the crystal lattice parameters and surface morphology of the polymorphs. These changes affect how water molecules interact with the crystal surface and penetrate into the lattice structure. The new polymorphic forms exhibit different surface areas, pore structures, and hydrogen bonding capabilities, resulting in reduced hygroscopicity while maintaining chemical stability.
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 new polymorphs provide enhanced solubility and stability, enabling effective pharmaceutical compositions for treating gastrointestinal inflammatory diseases like erosive gastroesophageal reflux disease (eGERD) with prolonged gastric acid control.
Implementation Method 1
Development of stable crystalline polymorphs of the hydrochloride salt of linaprazan glurate, specifically Forms 1 and 2, which exhibit higher solubility, lower hygroscopicity, and improved chemical stability, achieved through various crystallization techniques.
Data Source
AI summary
The present invention relates to polymorphs of the hydrochloride salt of 5-{2-[({8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridine-6-yl}carbonyl)-amino]ethoxy}-5-oxopentanoic acid (linaprazan glurate), more specifically Form 1 and Form 2 of the HCl salt of linaprazan glurate. The invention also relates to a process for the preparation of such polymorphs, to pharmaceutical compositions comprising such polymorphs, and to the use of these polymorphs in the treatment or prevention of gastrointestinal inflammatory diseases or gastric acid related diseases, in particular erosive gastroesophageal reflux disease (eGERD).