PC945 Crystalline Forms for Stable Aqueous Inhalation Delivery

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Solution Overview

Problem

Existing antifungal compounds, such as Compound I, face challenges in achieving effective topical administration to the lung due to poor crystalline forms that affect stability, solubility, and bioavailability, leading to inadequate drug concentrations and resistance issues.

Innovation Solution

Development of crystalline polymorphic Forms 1 and 2 of Compound I, which exhibit high melting points, physical robustness, chemical stability, and bioavailability when administered as an aqueous suspension by inhalation, allowing for effective topical treatment of mycoses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If existing antifungal compounds are administered orally or systemically, then the drug can reach the bloodstream, but the drug concentration at the site of infection (lung airways) is lower than in non-affected organs

Engineering Contradiction:

Improvedrug concentration at infection siteVSAvoidroute of delivery efficiency

Core Design Contradiction:

Quantity of substanceVSEase of operation

Solution Approach 1:

The patent introduces an inhaled aerosol formulation as an intermediary delivery system that transports the antifungal compound directly to the lung airways, bypassing the bloodstream and achieving higher local drug concentrations at the infection site

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If oral triazole medicines are used to treat invasive aspergillosis, then treatment can be provided, but the liver is exposed to significant drug levels causing toxicity and drug interactions

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidliver toxicity and drug interactions

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the drug delivery system into local (inhaled to lungs) and systemic components, allowing the antifungal to act primarily at the infection site while minimizing exposure to distant organs like the liver, thereby reducing toxicity and drug interactions

Inventive Principle:

Principle #1Segmentation

3Adaptability or versatility

If broad-spectrum triazole use is increased to treat resistant mycoses, then more infections can be treated, but resistant mycoses continue to emerge and spread

Engineering Contradiction:

Improvetreatment coverageVSAvoidresistance development

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent changes the delivery parameter from systemic to localized inhaled administration, achieving high local drug concentrations that can overcome resistance while limiting systemic exposure that drives resistance development

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12491182B2Polymorphs of triazole antifungal compound PC945

Publication Date: 2025.12.09 PULMOCIDE

AI summary

The invention relates to crystalline polymorphic manifestations of a compound of formula (I) and related aspects.