A new proposal for the development of sustainable generic DPI products based on respirable dose matching rather than being an exact copy of the reference
Giada Varacca1, Chiara Schianchi1, Aurora Squeri1, Mauro Citterio2, Marco Franza2 & Francesca Buttini1
1Food and Drug Department, University of Parma, Italy
2 Plastiape, a Berry Global company, Osnago, Italy
Summary
In contrast to the current strategy, which encourages generic manufactures to create “low performing” formulations in order to match the aerodynamic characteristics of out-of-date reference product, this work provides evidence in favour of an unconventional sustainable approach to create generics. Thanks to the advances in device and formulation, greater drug emitted, and respirable doses can be achieved with the possibility to load a lower nominal dose hence reducing the drug mass employed and the impact related to its synthesis and disposal.
The purpose of this project was to assess the reduction of the nominal dose of two types of exploratory generic formulations produced with two different technologies (by mixing in Turbula mixer and by spray drying process), coupled with RS01 inhaler as copies of the reference products. The reference products were Spiriva Handihaler, containing tiotropium bromide (TiB), and Serevent Diskus, containing salmeterol xinafoate (SX).
From the data obtained, it is possible to reduce the drug nominal dose of 30% and 50% for the TiB-InhaLac150_RS01 and TiB-Spray Dried (SD) with Leucine_RS01 formulations, compared to the reference product; rather, considering the SX-InhaLac150_RS01 and SX-SD with Leucine_RS01 formulations, it is possible to have a drug nominal dose reduction of 25% and 33% respectively.
This work represents a provocation to push us to think in a more “modern” and sustainable way but certainly it should be agreed by the regulatory authorities and the nominal dose reduction would have to be confirmed in vitro along with a clinical study showing efficacy and PK profile.