Eutectic Mixture for Pulmonary Drug Delivery

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Solution Overview

Problem

Current pharmaceutical compositions for treating respiratory diseases, particularly chronic obstructive pulmonary disease (COPD) and asthma, face challenges in delivering two pharmacologically active ingredients to the lung effectively, including issues with particle stability, agglomeration, and inconsistent delivery due to variations in surface properties and processing methods, which affect the efficacy and onset time of the drugs.

Innovation Solution

A pharmaceutical composition comprising a eutectic mixture of a long-acting β2 agonist and a long-acting muscarinic antagonist, formed through methods such as dissolving and removing solvents, forming melts, or mechanical comminution, to create particles with a lower melting point and increased solubility, enhancing delivery and interaction with lung surfactants.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If two pharmacologically active ingredients are delivered as separate solid crystalline particles, then particle stability is maintained, but dissolution rate and onset time are slow

Engineering Contradiction:
Improvedissolution rateVSAvoidparticle stability
Core Design Contradiction:
SpeedVSStability of the object's composition

Solution Approach 1:

The patent changes the physical state parameter of the drug particles from stable crystalline solid to less stable amorphous or liquid-like eutectic form. This parameter change increases surface energy and molecular mobility, thereby dramatically increasing dissolution rate and onset time while accepting reduced particle stability as a trade-off

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transition by forming a eutectic composition that melts at a lower temperature than the individual components. The eutectic mixture transitions from solid to liquid-like state at physiological temperature, enabling rapid dissolution and absorption while maintaining physical integrity during storage

Inventive Principle:
Principle #36Phase transitions

2Reliability

If two drugs are co-delivered to the lung, then synergistic therapeutic effects are achieved, but particle agglomeration and inconsistent delivery occur

Engineering Contradiction:
Improvedelivery consistencyVSAvoidparticle agglomeration
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent merges two separate drug particles into a single integrated eutectic particle system. The two pharmacologically active ingredients are combined at the molecular level in a eutectic composition, ensuring they remain together as a unified particle during inhalation and delivery, thereby preventing agglomeration and ensuring consistent co-delivery to the lung

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent creates a composite particle system where two different pharmacologically active ingredients form a eutectic composition with specific physical and chemical properties. This composite structure ensures compatible surface properties and prevents differential behavior during processing and delivery, eliminating agglomeration issues

Inventive Principle:
Principle #40Composite materials

3Quantity of substance

If eutectic composition is used to increase solubility, then dissolution rate improves, but manufacturing complexity increases

Engineering Contradiction:
ImprovesolubilityVSAvoidmanufacturing complexity
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent changes the compositional parameter by forming a eutectic mixture with specific ratios of two pharmacologically active ingredients. This parameter change results in a composition with lower melting point and higher solubility than the individual components, achieving improved dissolution rate through controlled formulation design

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes established eutectic formation principles from pharmaceutical science to create the composition. By applying known methods for forming eutectic mixtures (such as co-milling or solvent evaporation), the manufacturing process leverages existing technical knowledge rather than requiring entirely new manufacturing approaches

Inventive Principle:
Principle #26Copying

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 eutectic composition improves the delivery and efficacy of both active ingredients to the lung, increasing their solubility and dissolution rate, leading to faster onset of action and enhanced therapeutic effects by maximizing synergistic interactions with lung tissue.

Implementation Method 1

The unique property of a eutectic is that it has a lower melting temperature than that of either pure compound

Methodology Applied
Scientific EffectEutectic melting point depression: Melting

Implementation Method 2

When the eutectic composition is exposed to the gastrointestinal fluids, the soluble carrier dissolves rapidly, leaving the insoluble drug in an extremely fine state of subdivision

Methodology Applied
Scientific EffectDifferential solubility: Solvation

Data Source

PatentEP2741739B1Eutectic mixture for pulmonary administration
Publication Date: 2017.07.19 CIRCASSIA LIMITED
  • EP2741739B1 patent drawingFigure 1~2
  • EP2741739B1 patent drawingFigure 3~4
  • EP2741739B1 patent drawingFigure 5~6

AI summary

This invention provides a pharmaceutical composition comprising a eutectic composition of two pharmacologically active ingredients for delivery to the lung by inhalation. This invention also provides a pharmaceutical composition comprising a eutectic composition of two pharmacologically active ingredients for the treatment of respiratory disease.