Crystalline sGC Stimulator Forms for Consistent Drug Properties

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing sGC stimulators lack well-characterized solid forms that can lead to inconsistencies in drug properties such as solubility, dissolution rate, and bioavailability, posing challenges during clinical trials and commercialization.

Innovation Solution

Development of crystalline solid forms of Compound I, including polymorphs and solvates, with specific preparation methods to enhance stability and bioavailability, characterized by XRPD and FT-Raman spectra.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If amorphous or poorly characterized solid forms of sGC stimulators are used, then drug development can proceed without extensive solid form screening, but inconsistencies in solubility, dissolution rate, and bioavailability occur

Engineering Contradiction:

Improvetime for solid form screeningVSAvoidconsistency of drug properties

Core Design Contradiction:

Loss of timeVSReliability

Solution Approach 1:

The patent performs preliminary solid form characterization and selection during drug development, identifying and characterizing specific crystalline polymorphs and solvates of Compound I before clinical trials. This preliminary action establishes well-defined solid forms with consistent properties, preventing later inconsistencies in solubility, dissolution rate, and bioavailability that would require time-consuming rework.

Inventive Principle:

Principle #10Preliminary action

2Manufacturing precision

If multiple crystalline polymorphs and solvates are developed, then solubility and bioavailability can be optimized, but complexity in characterization and selection increases

Engineering Contradiction:

Improvecontrol of drug propertiesVSAvoidcomplexity of solid form characterization

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent systematically varies crystallization parameters such as solvent type, temperature, and concentration to generate different solid forms of Compound I. By controlling these parameters, the invention optimizes solubility and bioavailability while maintaining manageable complexity through structured characterization using techniques like XRPD, FT-Raman, and DSC to identify and differentiate the polymorphs and solvates.

Inventive Principle:

Principle #35Parameter changes

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 crystalline forms of Compound I provide consistent drug properties, improving solubility, stability, and bioavailability, reducing variability and enhancing therapeutic efficacy.

Implementation Method 1

Crystalline solid forms of Compound I are described herein. In one embodiment, the crystalline solid form of Compound I is polymorph Form A.

Methodology Applied

Scientific EffectCrystallisation: Crystallisation

Data Source

PatentUS20250282769A1Solid forms of an sgc stimulator

Publication Date: 2025.09.11 CYCLERION THERAPEUTICS INC

AI summary

The present disclosure relates to crystalline solid forms of a stimulator of soluble guanylate cyclase (sGC), Compound I. Also provided herein are methods for the preparation of these solid forms. The invention also relates to pharmaceutical formulations and dosage forms comprising these solid forms and their uses thereof, alone or in combination with one or more additional agents, for treating and/or preventing various diseases or disorders; these diseases or disorders are ones that may benefit from sGC stimulation or from an increase in the concentration of nitric oxide (NO) and/or cyclic guanosine monophosphate (cGMP).