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Article / 2019

Inhalation Drug Delivery: The Impact of Particle Size Reduction

Within the past few years, much has been learned about characterizing the particles used in inhalation therapies, with the goal of improving drug delivery to the lungs.

  • Andreia Lopes
  • Raquel Barros
  • Sergio Silva
Pharmaceutical Technology, 02 September 2019

Optimizing the manufacturing of these therapies requires avoiding particle interactions during size reducing, blending, and capsule filling, because these can affect the final product’s quality.

In an inhalation formulation, the physicochemical properties of size-reduced drug particles strongly affect the end product’s stability and performance. Previous studies reported that size-reduced APIs that had been milled using different techniques may present significant differences in terms of morphological and interfacial properties (1,2). Characterizing the particles’ surface properties is key to understanding API/excipient interactions and their impact on the final formulation performance.

Selecting the micronization technique is crucial for particles that are to be used in inhalation therapies, because it will determine the API’s properties. For inhalation delivery, a narrow and controlled particle size distribution (PSD) is key to improving and consistently delivering the aerodynamic performance. With a narrow PSD and Dv90<5µm, the fraction of particles that reach the lungs (FPF) will be higher.

These interactions depend on physicochemical characteristics of the particles, such as morphology, electrostatic charge, contact area, surface energy, carrier surface roughness, and relative humidity. Thus, the characterization of the particles’ surface properties becomes the key to understanding their surface-based phenomena, offering insights into interactiveforces and adhesion affecting the API, carrier and device. Several studies (2,3,4) have shown the importance of the particle’s properties to the efficacy of the formulation and its aerodynamic performance.

The objective of this work was to analyze and compare particle attributes (e.g., size, morphology, polymorphism, and surface properties) of two different corticosteroids that are intended for inhalation formulations. The materials were processed by both wet and dry milling.

Particle size-reduction techniques

Different size reduction approaches were evaluated...

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