Chemical Particle Characterization in Respiratory Drug Products

Particle size plays a particularly significant role in inhalable drug production, due to particles from 2-15 µm settling in the alveolus. Therefore, regulatory agencies and manufacturers alike follow strict regulations regarding proper sizing and chemical specific detection of the useful active pharmaceutical ingredient (API) particles, as well as in the tight control of foreign particles in inhalable and nasal inhalable.

Particle size plays a particularly compelling role in inhalable spray drugs - OINDP.
Morphologically directed Raman spectroscopy is used to determine the chemically specific particle size distribution (CSPSD). This has an important impact on bioequivalence, and is consequently used for de-formulation studies of originator products.

Foreign Particulate Matter in Inhalables

Early studies on Dry Powder Inhalers (DPI) showed that more than 95% of all foreign particles are organic (plastic and fibers) by origin, and therefore cannot be attributed correctly to any substance found through SEM/EDS analysis.

Particle size and shape data directs the Raman spectroscopy, and delivers a chemical specific particle size distribution. rap.ID offers the world’s most efficient technical solutions to provide rapid and relevant information in regards of the API, or contamination particles from 2-10 µm.

  • Foreign particle status of formulations, agents and excipients; foreign particle load in administered doses
  • Method development and validation of foreign particle studies
  • Routine foreign particle monitoring and release testing of nasal spray suspensions
  • Testing for particulate matter release on capsules and inhaler parts
  • Quality assurance and foreign particle analytics in inhalable drugs
  • Cleanliness analyses for incoming inspection of inhaler component parts

rap.ID’s contract testing services provide API and FPM identification method development and validation, within an extremely short timeline. Contact us today to streamline your new drug application, ANDA and NDA regarding FPM assessment.

Dry Powder Inhaler Data

An overview of particle materials found during a 15 year investigation on Dry Powder Inhalers in 6 different products.

Foreign particle analysis Foreign Particles in Dry Powder Inhalers
foreign particulate Matter analysis dry powder Inhaler Data

Main Sources of Foreign Particulate Matter Recovered while Simulating Use for Three DPIs Foreign Particulate Matter

Particle Composition Source
Cellulose Assembly and transport of device components
Polymers Particles generated during of the device.
Carbon Manufacturing, assembly and transport of device components
Protein Manufacturing and assembly, associated with the lactose carrier.

1. During our studies no significant amount of FPM that might be considered dangerous (such as asbestos) was found.

2.  In some cases we concluded that the contamination profiles in a dry powder inhaler was strongly dependent on sampling point (dose number) in the file time of the device.

3. In one example, after the first couple of actuations, the particles chemical nature changed from larger cellulose particles and fragments to smaller polymer particles.

4. Polymer particles were typically found to originate from the device itself.

5. Regardless of the device life-stage, the most prevalent contaminants were cellulose, polymers, carbon and proteins.

6. Particles can be generated during device usage.


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