A new paper from the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) provides valuable insight on laboratory performance testing for those developing and manufacturing aqueous nasal inhalation products. Focusing specifically on the measurement of aerodynamic particle/droplet size distribution (APSD) the new paper was developed by those working at the forefront of nasal drug product development and testing; it is freely available online here. The paper addresses the strengths and limitations of alternative methodologies and is valuable for anyone looking to understand how to use routine methods such as cascade impaction (CI) and laser diffraction (LD) to maximum advantage. The potential benefits of newer techniques such as Morphologically Directed Raman Spectroscopy (MDRS) are also discussed.
“As we note in the paper, nasal and orally inhaled products are usually grouped together but the associated particle/droplet sizing challenge is distinctly different,” said Mark Copley, CEO of Copley Scientific and one of the contributors. “For deposition in the nose we’re looking at a larger APSD, but with the risk of unintended deposition of fines in the lung. The need is for relevant, informative measurement across the whole APSD with CI and LD typically used in combination to cover the range of interest.”
The upswing in nasal drug product development over recent years has prompted scrutiny and improvement of the associated test methods. The paper begins with a summary of regulatory requirements for aqueous nasal inhalation products in the US, Europe and elsewhere and goes on to cover:
- CI methods for the assessment of small droplets (typically less than 10 microns) including strategies for extending the upper size limit of the technique and requirements for automated actuation.
- LD and alternative optical/imaging methods such as particle/droplet image analysis and particle image velocimetry for the measurement of droplets across the 20 - 200µm range typically targeted for intranasal drug delivery.
- the use of in vivo-predictive inlet ports to investigate regional deposition behaviour within the nose.
- Chemically distinctive imaging techniques such as Raman chemical imaging and MDRS which address the lack of chemical identification associated with optical methods.
IPAC-RS was established in 2000 to represent the orally inhaled and nasal drug product (OINDP) industry and ‘advance the science, and especially the regulatory science, of OINDPs’. By capturing state-of-the-art understanding from knowledgeable IPAC-RS members/associate members this new paper adds to the information available to the growing number of people seeking to capitalise on the intrinsic benefits of intranasal drug delivery. Download it here.