Development challenges for hybrid applications of DPIs. Could IVIVC tools predict in vivo conditions? A case study with Elpenhaler device.  

Stavroula Rozou¹, Ergina Pentafragka¹, Magdalene Kalovidouri¹

¹ELPEN Pharm.Co.Inc., 95 Marathonos Ave., Pikermi, 19009, Greece

Summary

It is a common practice to combine various techniques in the effort to predict the clinical outcome of OIDPs. An official regulatory framework is not yet available, but efforts are made to unscramble the fate of the drugs in the respiratory tract. Prediction can be more risky when it comes to comparison of inhalers with different geometries and aerodynamic performance. This being the case, the development and comparison of DPI products are challenged with the use of two different versions of Elpenhaler devices that have entirely different principle of use from the reference product (blisters vs capsules). The challenge was the prediction of clinical similarity of these products by combining in vitro methodologies with computational models. In vitro results were partially indicative but not reliable of the clinical outcome. Anatomic models and patient simulated flow rates were proved to be more accurate as per the information provided and gave more close results to the actual bioequivalence outcome. Nevertheless, the biggest uncertainty remains the actual users and all their associated individualities. To this end, very good knowledge of the inhalers performance, adequate user training and very close monitoring of the clinical study could increase the probability of a successful outcome.

Key Message

IVIVC can be proved challenging when inhalers that perform differently are compared. For such a development exercise, we evaluated the use of in vitro techniques combined with computational models to predict the in vivo outcome. We obtained promising results, but extensive validation is required until these can be safely used.