Jolyon Mitchell has long been a leading voice in OINDP development and analysis through numerous publications and through service to multiple organizations, including EPAG, and contributions to pharmacopoeias including the USP and Ph. Eur. He plans to retire from his current position with Trudell Medical International in September 2013. This is the 2nd article in a 3-part series.
Q: What have been some of the most significant changes in inhaler analysis over the years?
A: At TMI we have been pioneering new ways of thinking about the evaluation of inhalers which certainly weren’t common knowledge when I joined the company in 1994. For example, at that time, the pharmacopoeias wouldn’t have anything to do with spacers and valved holding chambers because they were seldom an integral part of a marketed drug product.
Nowadays, both the pharmacopeias and standard-setting bodies such as the Canadian Standards Association and the International Standards Organization include these add-on devices within their remit. This change has come about because of a general recognition that they are a key part of the drug delivery process when a patient uses an add-on with their inhaler.
There are other paradigm shifts that have resulted in improvements to the way we test inhaled drug products. In one particular example that comes to mind, it was crucial a few years ago to get stakeholders to understand that the cascade impactor is not a lung simulator. Unfortunately, many regulators were of the opinion that the opposite was true.
This misunderstanding was not helped by the existence of a widely publicized diagram from an impactor manufacturer that showed drug particles collecting at the different locations within the apparatus directly linked to specific sites in the respiratory tract.
In response, Dr. Craig Dunbar and I co-authored a rebuttal to this way of thinking (‘The Interpretation of Data from Cascade Impactors’, J. Aerosol Med. 2005, 18(4), 439-451.) to get across that particle size selectivity is a key characteristic that is much greater in the cascade impactor than in the various regions of the human respiratory tract.
Although you can certainly get useful information from the cascade impactor about the inhaler-produced aerosol aerodynamic particle size distribution (APSD), it is misleading to link specific stages with one particular sub-region of the respiratory tract. I think that this knowledge is now in the general understanding of all stakeholders, since this message has come out repeatedly in this congress as well as in the past few years at other similar venues.
