Inhalation Composition Blending for Aerodynamic Diameter Control

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Solution Overview

Problem

Current pharmaceutical compositions for inhalation therapy face challenges in tuning the aerodynamic diameter of particles for multiple active substances to ensure precise delivery to different regions of the respiratory tract, leading to interactions and instability, especially in combination therapies.

Innovation Solution

A method involving preblending each active ingredient with a specific excipient, followed by a main blending process with varying intensity, to achieve independent control over the aerodynamic diameter and reduce interactions, enhancing stability and homogeneity, using excipients with different d50 values and weight ratios.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If multiple active substances are blended together in a single process, then the manufacturing process is simple, but the aerodynamic diameter cannot be precisely controlled for each substance

Engineering Contradiction:
Improveblending process simplicityVSAvoidaerodynamic diameter control
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent divides the blending process into separate stages: first blending each active substance with its designated excipient independently to control aerodynamic diameter, then combining the preblends in a second blending step. This segmentation allows precise control of particle characteristics for each active substance while maintaining overall manufacturability.

Inventive Principle:
Principle #1Segmentation

2Ease of manufacture

If active ingredients are blended with excipients in a single step, then the process is straightforward, but interactions and instability occur

Engineering Contradiction:
Improveprocess simplicityVSAvoidformulation stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The formulation process is segmented into distinct blending stages where each active ingredient is separately combined with its assigned excipient. This prevents unwanted interactions between different active substances while maintaining formulation stability, and the separate preblends are then combined in a controlled second step.

Inventive Principle:
Principle #1Segmentation

3Stability of the object's composition

If the same excipient is used for all active ingredients, then the formulation is homogeneous, but the aerodynamic properties cannot be optimized for each substance

Engineering Contradiction:
Improveformulation homogeneityVSAvoidaerodynamic diameter tuning
Core Design Contradiction:
Stability of the object's compositionVSManufacturing precision

Solution Approach 1:

The patent applies different excipients to different active ingredients based on their specific aerodynamic requirements. Each active substance is blended with an excipient selected to optimize its particular aerosolization characteristics, allowing local optimization of aerodynamic properties while maintaining overall formulation homogeneity through controlled blending.

Inventive Principle:
Principle #3Local quality

4Reliability

If more active ingredient is used to ensure adequate delivery, then the therapeutic effect is sufficient, but the amount of active ingredient needed increases

Engineering Contradiction:
Improvetherapeutic effect reliabilityVSAvoidactive ingredient amount
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent utilizes aerosolization technology to deliver active ingredients in respiratory-sized particles (0.5-10 μm) that can be efficiently transported to the lungs. By optimizing the aerodynamic diameter through excipient selection and blending parameters, the formulation achieves reliable therapeutic delivery with reduced active ingredient quantities.

Inventive Principle:
Principle #29Pneumatics and hydraulics

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

This approach allows for precise adjustment of particle entry into the respiratory tract, reducing active ingredient amounts needed for the same effect, improving homogeneity and stability, and enhancing therapeutic efficacy.

Implementation Method 1

each different active ingredient is blended in a preblending procedure with a suitable excipient to which said active ingredient adheres

Methodology Applied
Scientific EffectAdhesion: Adhesive

Implementation Method 2

a dose of the pharmaceutical composition is positioned in an aerosolization chamber, where it is aerosolized and, hence, dispersed into respirable particles by airflow supplied by the patient's inspiration effort

Methodology Applied
Scientific EffectAerosolization: Aerosol

Implementation Method 3

medicament particles deposit in specific areas of the pulmonary system based upon the aerodynamic size of the particles and the flow rate of the air within which they are entrained

Methodology Applied
Scientific EffectParticle deposition: Deposition (physical)

Data Source

PatentEP2398464B1Pharmaceutical composition for inhalation
Publication Date: 2016.11.02 SANOFI SA(FR)
  • EP2398464B1 patent drawingFigure 1
  • EP2398464B1 patent drawingFigure 2
  • EP2398464B1 patent drawingFigure 3

AI summary

The present invention relates to a pharmaceutical composition for inhalation. The invention is further directed to a method for setting the performance characteristics of such a pharmaceutical composition and the use of such a composition in the treatment of asthma, COPD, allergies, infectious diseases and diseases of the cardiovascular system.