The combination of an innovative dry powder for inhalation and a standard cisplatin-based chemotherapy in view of therapeutic intensification against lung tumours.

Cisplatin is one of the most commonly used chemotherapy in lung cancer despite its high nephrotoxicity leading to an administration only every 3-4 weeks. This study is the first report of a preclinical investigation of therapeutic intensification combining a cisplatin dry powder for inhalation (CIS-DPI) with an intravenous (iv) cisplatin-based treatment. CIS-DPI with 50% cisplatin content (CIS-DPI-50) was developed using lipid excipients through scalable processes (high-speed and high-pressure homogenization and spray-drying). CIS-DPI-50 showed good aerodynamic performance (fine particle fraction of ~ 55% and a mass median aerodynamic particle size of ~ 2 µm) and a seven-fold increase and decrease in Cmax in the lungs and in plasma, respectively, in comparison with an iv cisplatin solution (CIS-iv) in healthy mice. Finally, the addition of CIS-DPI-50 to the standard cisplatin/paclitaxel iv doublet increased the response rate (67% vs 50%), decreased the tumour growth and prolonged the median survival (31 vs 21 days), compared to the iv doublet in the M109 lung carcinoma model tending to demonstrate a therapeutic intensification of cisplatin.

Impact of capsule type on aerodynamic performance of inhalation products: A case study using a formoterol-lactose binary or ternary blend.

The aerodynamic performance of a dry powder for inhalation depends on the formulation and the dry powder inhaler (DPI). In the case of capsule-based DPIs, the capsule also plays a role in the powder aerosolisation and the dispersion of the micronized drug during the inhalation. This study evaluated the impact of gelatine capsules (Quali-G™ and Hard Gelatine Capsules for DPIs), cold-gelled hypromellose (HPMC) capsules (Quali-V®-I and Vcaps®) and thermal-gelled HPMC capsules (Vcaps®Plus) from Qualicaps® and Capsugel® respectively, on the delivered dose (DD), fine particle dose (FPD), and capsule retention for formoterol-lactose binary and ternary blends. This study used a low resistance Axahaler® DPI based on the RS01 design (Plastiape, Italy). Similar trends were observed with the different capsule types that packaged both dry powder formulations. The highest DD and FPD and the lowest formoterol capsule retention were observed with cold-gelled HPMC capsules such as Quali-V-I® and Vcaps®, without significant differences between these capsules (p > 0.05, one-way ANOVA with Newman-Keuls post-hoc test) for both dry powders. Therefore, the capsule composition and manufacturing process have an influence on aerodynamic performance. In addition, the ternary blend showed higher DDs and FPDs but also higher capsule retention in comparison to the binary blend.

Proposed algorithm for healthcare professionals based on product characteristics and in vitro performances in different use conditions using formoterol-based marketed products for inhalation.

Healthcare professionals require an easy algorithm for selecting the most appropriate inhalation product for each patient at the beginning of a treatment. As a case study, we selected five marketed formoterol products: Foradil® and Formagal®, capsule-based dry powder inhalers (DPIs), Novolizer® Formoterol and Oxis®, reservoir-based DPIs and Formoair®, a pressurized metered dose inhaler. We generated an algorithm based on device properties (i.e. device handling, feedback and remaining dose/end of product indication) and in vitro aerodynamic performances (i) along the product use life in optimal conditions, (ii) at different airflows and (iii) after exposing pre-loaded doses to 40°C and 75% relative humidity for 4h. Based on these results, an algorithm was built where Formoair and Formagal can be proposed when there is high risk of humidity and for patients presenting suboptimal or optimal airflows. When no risk of humidity is present, Formoair, Foradil, Formagal and Novolizer Formoterol equipped with a trigger valve could be proposed for patients presenting suboptimal airflows. When no risk of humidity is present and for patients presenting optimal airflow, all products, including Oxis, could be proposed. Ultimately, the optimal inhalation product will be selected after checking the patient's preference and capacity for correct device handling and inhalation technique.