Dry Powder Inhaler Particle Surface Modification

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is a challenge in preparing pharmaceutical compositions in dry powder form for efficient delivery to the lung, as particles below 5 microns in aerodynamic diameter improve lung deposition but deagglomeration efficiency declines, and existing methods using surface-modified nanoparticles face difficulties in handling and separating these particles without adverse effects.

Innovation Solution

The method involves mixing active pharmaceutical ingredients with media particles having surface-modified nanoparticles, separating them to deposit the nanoparticles on the active ingredient particles, enhancing flowability and dispersibility, and using these particles in dry powder inhalers with improved respirable fractions and delivery efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If particle size is reduced below 5 microns to improve lung deposition, then lung deposition efficiency is improved, but deagglomeration efficiency declines markedly

Engineering Contradiction:

Improvelung deposition efficiencyVSAvoiddeagglomeration efficiency

Core Design Contradiction:

Manufacturing precisionVSProductivity

Solution Approach 1:

The patent introduces carrier particles as an intermediary medium to solve the contradiction between small particle size and deagglomeration efficiency. The active pharmaceutical ingredient is adsorbed onto carrier particles, which serve as a mediator between the drug and the delivery system. This allows the drug to be delivered in a respirable size while the carrier provides the necessary bulk for effective deagglomeration and delivery.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of operation

If surface-modified nanoparticles are added to improve flowability, then flowability characteristics are improved, but handling and separation challenges arise

Engineering Contradiction:

Improveflowability characteristicsVSAvoidhandling and separation complexity

Core Design Contradiction:

Ease of operationVSDevice complexity

Solution Approach 1:

The patent modifies the surface properties of nanoparticles through chemical modification to change their interaction characteristics. By altering surface parameters (hydrophobicity, charge, functional groups), the nanoparticles achieve improved flowability and controlled interaction with carrier particles, enabling easier handling and separation while maintaining enhanced flow characteristics.

Inventive Principle:

Principle #35Parameter changes

3Productivity

If small respirable drug particles are adsorbed onto larger inert carrier particles to provide bulk deagglomeration, then deagglomeration is improved, but additional energy is required to release the drug from the carrier surface

Engineering Contradiction:

Improvedeagglomeration efficiencyVSAvoidenergy required for drug release

Core Design Contradiction:

ProductivityVSUse of energy by moving object

Solution Approach 1:

The patent applies local quality modification by selectively modifying the surface properties of carrier particles in specific regions or to specific degrees. This creates zones of varying drug release characteristics, allowing controlled energy requirements for drug release while maintaining overall deagglomeration efficiency. The surface modification is tailored to local needs rather than uniform modification throughout.

Inventive Principle:

Principle #3Local quality

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 method significantly improves the respirable fraction and delivery efficiency of active pharmaceutical ingredients by up to 75% and 50% respectively, while maintaining the active ingredient's integrity and stability without using liquids that could adversely affect it.

Implementation Method 1

surface-modified nanoparticles can be effectively applied to a micronized active pharmaceutical ingredient by mixing the active ingredient with media particles having surfaces with the surface-modified nanoparticles deposited on the surfaces

Methodology Applied

Scientific EffectAdsorption: Adsorption

Implementation Method 2

The media particles are selected such that they can be separated from the active ingredient

Methodology Applied

Scientific EffectDensity-based separation: Density Gradient

Data Source

PatentEP2309984B1Method of making a dry powder pharmaceutical composition

Publication Date: 2018.04.11 3M INNOVATIVE PROPERTIES CO

AI summary

A method of making active pharmaceutical ingredient particles with surface-modified nanoparticles deposited on the particles' surfaces, the method comprising: providing a plurality of media particles having surfaces with the surface-modified nanoparticles deposited on the surfaces; mixing the plurality of media particles with the active ingredient particles, both of which are in dry form, to provide active ingredient particles having surfaces with the surface-modified nanoparticles deposited on the surfaces; and separating the plurality of media particles from the active ingredient particles having surfaces with the surface-modified nanoparticles deposited on the surfaces is disclosed.