Influence of mannitol carrier morphology on the DPI performance of different APIs

Mathias Mönckedieck, Jens Kamplade, Peter Walzel, Nora Urbanetz, Hartwig Steckel, Regina Scherließ

Dry powder inhalers (DPIs) mostly utilise the well-established system of coarse carrier particles (> 50 μm) with good flow properties and active pharmaceutical ingredients (APIs, < 5μm), which are attached to the carrier surface to overcome dosing problems of the small cohesive drug particles when used alone. This study was employing spray drying with a special focus on particle size and particle morphology to generate batches with tailored mannitol carrier particles of 50 – 70 μm. A design of experiments with the factors drying temperature and rotary speed was applied to obtain a wide set of different carrier particles. A choice of six mannitol batches was selected for the preparation of interactive mixtures with both the hydrophilic model drug salbutamol sulphate (SBS) and the lipophilic model drug budesonide. Aerodynamic characterisation was performed with a Novolizer® by using the Next Generation Pharmaceutical Impactor to obtain the Fine Particle Fraction (FPF). Three different SBS qualities were tested. Particle size was found to have a huge impact on the FPF due earlier impaction of larger particles. Additionally, aerodynamic characterisation detected a strong dependence of carrier morphology and FPF of the hydrophilic SBS, which in turn reveals the possibility to control the FPF by the preparation of tailor-made carrier surfaces. The dry powder inhaler performance of lipophilic budesonide was not affected by morphology, but exhibited noticeably higher FPFs for all chosen mannitol batches compared to SBS leading to the assumption that SBS is adhered tighter due to its possibility to build hydrogen bonds.

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