Dry Powder Inhaler Formulation for Corticosteroid and Beta-2 Agonist Delivery
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Solution Overview
Problem
Dry powder inhalers face challenges in delivering a therapeutically equivalent formulation of corticosteroids and beta-2 adrenergic drugs compared to pressurized metered dose inhalers, particularly in achieving high lung deposition and uniform distribution, and are difficult for elderly and pediatric patients to use due to actuation synchronization issues.
Innovation Solution
A process for preparing a dry powder formulation for dry powder inhalers comprising a mixture of fine and coarse alpha-lactose monohydrate particles with formoterol fumarate and beclometasone dipropionate, where the fine particles have a specific particle size distribution and magnesium stearate coating, ensuring high respirable fractions and improved reproducibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If pMDI formulations are used to deliver corticosteroids and beta-2 adrenergic drugs, then high lung deposition and uniform distribution are achieved, but elderly and pediatric patients have difficulty synchronizing actuation with inspiration
Solution Approach 1:
The invention divides the single actuation step of pMDI into two separate steps: first the patient performs a normal inhalation to activate the DPI mechanism, then continues inhalation to receive the medicated powder. This segmentation removes the synchronization requirement while maintaining delivery effectiveness.
Solution Approach 2:
The DPI device is designed to automatically activate and deliver the medicated powder during the patient's normal inhalation flow, without requiring the patient to perform additional actions or synchronize timing. The device self-activates based on the inhalation itself.
2Ease of operation
If dry powder formulations are used in DPIs, then actuation synchronization issues are resolved, but achieving therapeutically equivalent lung deposition compared to pMDI is difficult
Solution Approach 1:
The invention optimizes critical parameters including particle size distribution (MMAD 1.5-3.0 micrometers), flow rate characteristics (30-60 L/min), and device geometry to ensure the dry powder formulation achieves lung deposition characteristics therapeutically equivalent to pMDI formulations.
Solution Approach 2:
The formulation uses a composite approach combining the dry powder medicament with carefully controlled carrier particles and excipients to optimize aerosolization performance and lung deposition, achieving therapeutic equivalence despite the different delivery mechanism.
3Quantity of substance
If micronized particles are used in dry powder inhalers, then respirable fraction is increased, but volumetric contribution becomes an obstacle to designing therapeutically equivalent formulations
Solution Approach 1:
The invention carefully controls the particle size distribution parameters, specifying that 10-90% of particles have a mass median aerodynamic diameter of 1.5-3.0 micrometers, to maximize the respirable fraction while managing the volumetric contribution of micronized particles in the formulation.
Data Source
AI summary
The invention relates to a dry powder formulation comprising a corticosteroid and a beta2-adrenergic drug in combination, its process of preparation, and therapeutic uses thereof.