Carrier Particle Conditioning for Dry Powder Inhalers

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Solution Overview

Problem

Dry powder inhalation formulations for respiratory conditions face challenges with electrostatic charging during manufacturing, leading to drug loss, segregation, and agglomeration, which affects flow properties and homogeneity, and thus the reproducibility and accuracy of the delivered dose.

Innovation Solution

A process involving co-micronization of excipient and additive particles, followed by conditioning at specific relative humidity and temperature conditions to reduce electrostatic charges, improving flow properties and homogeneity by mixing these particles with coarse excipient particles and active ingredients.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If dry powders are processed during manufacturing (milling, mixing, transport, filling), then the powder is prepared for inhalation formulation, but electrostatic charges accumulate leading to drug loss, segregation, and agglomeration

Engineering Contradiction:

Improvepowder processingVSAvoidelectrostatic charges

Core Design Contradiction:

Ease of manufactureVSObject-generated harmful factors

Solution Approach 1:

A conditioning step is introduced as an intermediary process between powder preparation and inhalation formulation. The powder is exposed to controlled humidity conditions (e.g., 25-75% relative humidity for 1-24 hours) which acts as a mediator to dissipate electrostatic charges accumulated during manufacturing operations, thereby preventing drug loss, segregation, and agglomeration without affecting the manufacturing process itself

Inventive Principle:

Principle #24Intermediary (Mediator)

2Manufacturing precision

If electrostatic charges are reduced through conditioning, then flow properties and homogeneity improve, but additional processing time is required

Engineering Contradiction:

Improvedose homogeneityVSAvoidconditioning time

Core Design Contradiction:

Manufacturing precisionVSLoss of time

Solution Approach 1:

The conditioning process utilizes controlled changes in environmental parameters (humidity and temperature) to reduce electrostatic charges. By optimizing these parameters within specific ranges (e.g., 25-75% RH, 1-24 hours), the process achieves effective charge reduction and improved dose homogeneity while minimizing the additional time required compared to unconditioned powders

Inventive Principle:

Principle #35Parameter changes

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 process significantly reduces electrostatic charges, enhancing the flow properties, homogeneity, and reproducibility of the delivered dose, while maintaining the stability of the active ingredients, and improving the respirable fraction of the formulation.

Implementation Method 1

the co-micronised particles of step a) are first conditioned by exposure to a relative humidity of 50-75% at room temperature for a time comprised between 24 and 60 hours

Methodology Applied

Scientific EffectHumidity conditioning: Absorption (physical)

Implementation Method 2

a process for preparing carrier particles for dry powder formulation for inhalation... having reduced electrostatic charges

Methodology Applied

Scientific EffectElectrostatic charge reduction: Electrostatics

Data Source

PatentEP2560611B1"process for providing particles with reduced electrostatic charges"

Publication Date: 2018.01.03 CHIESI FARMACEUTICI SPA

Figure 1
Figure 2

AI summary

The invention concerns a process for preparing carrier particles for dry powder formulations for inhalation having reduced electrostatic charges. The invention also concerns the carrier particles thereof.