Budesonide 21-Phosphate Salts for Stable Nebulizer Delivery

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Solution Overview

Problem

Budesonide, a glucocorticoid steroid, is virtually insoluble in water and has stability issues in hydroalcoholic solutions, making it unsuitable for delivery via electric nebulizers, and existing combinations with β2 adrenergic agonists do not fully address allergen-induced airway dysfunctions.

Innovation Solution

Development of budesonide 21-phosphate salts, particularly with Formoterol, to enhance solubility and synergistic therapeutic effects, formulated into pharmaceutical compositions for inhalation or oral administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If budesonide is used in hydroalcoholic solutions, then solubility is improved, but stability deteriorates due to decomposition

Engineering Contradiction:

ImprovesolubilityVSAvoidstability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical form of budesonide from free acid to phosphate ester, fundamentally altering its solubility and stability parameters. This parameter change enables the compound to be stable in aqueous solutions while maintaining therapeutic efficacy, resolving the contradiction between solubility and stability.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The phosphate group acts as an intermediary structure that bridges the hydrophobic budesonide core with aqueous environments. This intermediary phosphate moiety enables compatibility with water-based formulations while preserving the active pharmacological properties of budesonide.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If budesonide is administered as conventional formulation, then therapeutic effect is achieved, but delivery via electric nebulizer is not possible due to solubility and stability issues

Engineering Contradiction:

Improvetherapeutic effectVSAvoiddelivery method compatibility

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

By changing budesonide to its phosphate ester form, the physical-chemical parameters are modified to enable compatibility with nebulizer delivery systems. The compound can now be formulated in aqueous solutions suitable for pneumatic inhalation devices while maintaining therapeutic reliability.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If combination of ICS and LABA is used, then therapeutic advantage is enhanced, but existing combinations do not fully address allergen-induced airway dysfunctions

Engineering Contradiction:

Improvetherapeutic advantageVSAvoidefficacy against allergen-induced airway dysfunction

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates a composite pharmaceutical formulation combining budesonide phosphate ester with formoterol. This composite approach leverages the anti-inflammatory properties of the glucocorticoid and the bronchodilator effects of the β2-agonist to provide comprehensive control of both baseline asthma and allergen-induced airway dysfunctions.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentEP4126898B1Budesonide 21-phosphate salts and pharmaceutical compositions containing the same

Publication Date: 2025.07.23 GENETIC SPA

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AI summary

The present invention relates to salts of budesonide 21-phosphate with β2 adrenergic agonists, preferably with formoterol, pharmaceutical compositions containing the same and the use thereof in the treatment of respiratory inflammatory pathologies, obstructive pathologies and allergen-induced airway dysfunctions. The invention further relates to the process for preparing said salts.