DDL 2017: My 3 Takeaways
December 27, 2017
An other year, an other Drug Delivery to the Lungs conference. Time to take the pulse of the inhaled drug delivery world. What was fun? New? Eye catching? Here are my 3 takeaways. This is a biased selection, a personal opinion, a whim; with 25 lectures and 82 posters, it has to be.
Connecting devices to phones, monitoring patients, improving their compliance has been fashionable for a number of years. “Telehealth” solutions mostly consist in chips fitted to devices to measure a number of parameters and relay them simultaneously or allow for a later download on a measuring device, inc. phones and tablets. Measured parameters include time, date, location, device orientation, actuation number, breath characteristics, atmospheric conditions etc. Each parameter increases the price of the chip, sometimes valuably I am told. Clement Clark who over the years has designed a number of streamlined inhaler aids, has come up with a clever and possibly cheap solution to patient monitoring. Gone are the expensive chips and in is a whistle attachment to place on top of a pMDI inhaler. The contraption emits a sound of variable pitch when the patient inhales, a sound that can be recorded via the microphone of a phone. The recorded sound-track indicates in one simple measurement: dose actuation and breath speed via the pitch of the whistle. How clever!, no electronics, a simple mechanical whistle, what looked like 2 bits of plastics, and a phone. Tuning breath characteristics to a whistle pitch appealed to musical fibre. At last a cheap and digital solution. Let’s hope it flies (1).
My second takeaway is the work on DPI de-aggregation presented by Kyrre Thalberg. Kyrre has long been studying DPI formulations. He has shifted his interest to CFD-DEM in-silico analysis of DPI mixtures to probe the dose emptying and dispersion from a dry powder inhaler mixture. This is reminiscent of the work performed by Shur et al. and Tibbatts et al. a few years ago on AFM+video CFD+PSD analysis, under a new angle and with some quantification. Kyrre and his team are going back to Phys-Chem basics with Van-der-Waals particle-particle interactions and attempts to understand carrier-fine API particles interactions vs. fine particle fractions. In addition, CFD modelling looks at the emptying of a theoretical inhaler and particles deposition within. Designing a Hamaker constant fit to describe lactose-API interactions is hard, not least because of the irregularity of the particles. It would be easy to describe the shortcoming of the approach, but it does provide a glimpse of the mechanisms at play in DPI formulation aerosolisation. As the carrier-API interactions become stronger the FPF comes down and so does the fine particle retention in the device. That at least is consistent with experience. Let’s watch what Kyrre does with this model and how it will integrate collisions, as it is one of the major forces during aerosolisation (2).
My third and last takeaway is about Q3. The concepts surrounding bio-equivalence requirements for inhaled products are well established. To be bio-equivalent products must be qualitatively (Q1) and quantitatively (Q2) equivalent, as well as use similar devices, have similar in vitro deposition profiles and have similar in vivo-responses (PK and PD). A new concept has crept in: Q3 equivalence. This has been lingering on for a number of years. Farias et al. gave it some flesh in their 2 posters (3, 4), one on DPIs and the other on Nasal sprays. Q3 refers to the microstructure of a formulation: the way particle aggregates form in DPIs or nasal products and how these clusters influence API dissolution and bio-availability. They developed combination methods, dubbed in-vitro orthogonal approaches, to probe formulations, identify formulation structural characteristics and relate them to product performance. This enabled them to justify performance differences between Seretide pMDI and Advair DPI for instance. They used a combination of Morphology Directed Raman Spectrometry + Dissolution testing. This is very similar to the work presented by Jetzer et al. (5, 6) who used Single Aerosol Mass Spectrometry + NGI + Electrostatic to prove a similar point. Q3 here we come! Let’s hope it does not become a requirement, because this could increase the price of generic products beyond economic viability.
DDL 2017: you did a good job. Glad to have joined you. Great fun. And thank you for your invitation to talk.
About Aedestra (www.aedestra.com): Aedestra is an inhaled product development company. We develop inhaled dosage forms: DPI, pMDI, Nasal, Nebule and SoftMist: Generics in particular. Aedestra can help you develop the right product in the right way by providing strategic and technical expertise. Get in touch now to expand and develop your inhaled portfolio: www.aedestra.com.
(1) DDL 2017 poster: “Whistle training aid and smartphone App. provide objective data” by Mark Sanders & Elizabeth Crawford. https://aerosol-soc.com/abstracts/whistle-training-aid-smartphone-app-provide-objective-data/; see also https://www.haag-streit.com/clement-clarke/.
2) DDL 2017 lecture: “Simulation of the Dose from a Dry Powder Inhaler” by Kyrre Thalberg, Johan Remmelgas, Duy Nguyen, Ingela Niklasson Björn & Berend vad Wachem. https://aerosol-soc.com/abstracts/simulation-dose-dry-powder-inhaler/.
(3) DDL 2017 poster: “Investigating the microstructure of dry powder inhalers using orthogonal analytical approaches” by Gonçalo Farias, William Ganley, Debbie Huck-Jones, Paul Kippax, Jagdeep Shur & Robert Price. https://aerosol-soc.com/abstracts/investigating-microstructure-dry-powder-inhalers-using-orthogonal-analytical-approaches/.
(4) DDL 2017 poster: “Investigating orthogonal in vitro analytical approaches to demonstrate bioequivalence of nasal suspension formulations” by Gonçalo Farias, Robert Price Debbie Huck-Jones, & Jagdeep Shur. https://aerosol-soc.com/abstracts/investigating-orthogonal-vitro-analytical-approaches-demonstrate-bioequivalence-nasal-suspension-formulations/.
(5) DDL 2017 poster: “Particle Interactions of Fluticasone Propionate and Salmeterol Xinafoate in Advair Diskus” by Martin Jetzer, Bradley Morrical, David Fergenson & Georgios Imanidis. https://aerosol-soc.com/abstracts/particle-interactions-fluticasone-propionate-salmeterol-xinafoate-advair-diskus/.
(6) DDL 2017 poster: “The Mechanism of Magnesium Stearate to Modify Aerosol Performance in Dry Powder Inhaled Formulations” by Martin Jetzer, Bradley Morrical, Marcel Schneider & Georgios Imanidis. https://aerosol-soc.com/abstracts/mechanism-magnesium-stearate-modify-aerosol-performance-dry-powder-inhaled-formulations/.