Dry Powder Inhaler Particle Size Control
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Solution Overview
Problem
Inhalable β2-agonists used for treating respiratory diseases often cause cardiac side effects due to systemic exposure, and combination products with corticosteroids complicate dose control, particularly for β2-agonists with narrower therapeutic windows.
Innovation Solution
A dry powder inhaler with a cyclone deagglomerator and a β2-agonist formulation having a narrowly defined particle size distribution, specifically d90 values between 3.5-6 microns, reduces systemic exposure and minimizes cardiac side effects, using jet milling to produce particles with controlled size and a lactose carrier for effective lung deposition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If β2-agonists are administered via inhalation to treat respiratory diseases, then therapeutic effect is achieved, but cardiac side effects occur due to systemic exposure
Solution Approach 1:
The patent changes the particle size parameter of the β2-agonist from conventional fine micronisation (d90 < 3.5 µm) to a coarser distribution (d90 = 3.5-6 µm). This parameter change reduces systemic absorption and cardiac side effects while maintaining pulmonary therapeutic efficacy through optimized lung deposition characteristics
Solution Approach 2:
The patent creates a localized effect by optimizing particle size for lung-specific deposition. The coarser particle size distribution ensures particles deposit primarily in the lungs where they are needed, reducing systemic exposure and cardiac side effects while maintaining local therapeutic concentration
2Ease of operation
If particles are micronised to small size (1-5 microns) for lung inhalation, then delivery to lungs is effective, but particles deposit in throat and are swallowed causing systemic exposure
Solution Approach 1:
The patent modifies the particle size parameter from fine micronisation (1-5 µm) to a coarser distribution (d90 = 3.5-6 µm). This change reduces throat deposition and swallowing, thereby minimizing systemic exposure while maintaining effective lung delivery through optimized aerodynamic properties
3Ease of operation
If combination products are used to improve patient convenience and compliance, then patient compliance improves, but control over individual dose is reduced
Solution Approach 1:
The patent segments the combination product into separate dosage forms or separate actuation mechanisms for each active ingredient. This allows independent dosing control of the β2-agonist and corticosteroid while maintaining the convenience of a single inhaler device, enabling precise control over the β2-agonist dose to avoid exceeding the narrow therapeutic window
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 solution significantly reduces systemic exposure to β2-agonists, minimizing cardiac side effects and ensuring effective delivery to the lungs while maintaining therapeutic efficacy, as demonstrated by reduced Cmax in pharmacokinetic studies.
Implementation Method 1
The particle size of the β2-agonist powder is measured by laser diffraction as a dry dispersion, e.g. in air, such as with a Sympatec HELOS/BF equipped with a RODOS disperser
Implementation Method 2
a cyclone deagglomerator for breaking up agglomerates of the dry powder medicament
Implementation Method 3
The particle size of the β2-agonist powder is measured by laser diffraction as a dry dispersion
Data Source
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AI summary
The present invention provides a dry powder inhaler comprising: a reservoir containing a dry powder formulation and an arrangement for delivering a metered dose of the medicament from the reservoir; and a delivery passageway for directing an inhalation-induced air flow through a mouthpiece, the delivery passageway extending to the metered dose of medicament, wherein the formulation comprises an inhalable β2-agonist having a particle size distribution of d10 <1 µm, d50 = 1-3 µm, d90 = 3.5-6 µm and NLT 99% <10 µm and a lactose carrier.