Tihana Baniček1, 4, Valerio Todaro2, Alessandro Cavecchi2, Eleonore Fröhlich1, 3, Andreas Zimmer4, Ožbej Zupančič1 & Sharareh Salar-Behzadi1, 4
1RCPE GmbH, Inffeldgasse 13, 8010 Graz, Austria
2CHIESI Farmaceutici S.p.A. Via Palermo, 26/a 43122 Parma, Italy
3Medical University of Graz, Center for Medical Research, Stiftingtalstraße 24, 8010 Graz, Austria
4University of Graz, Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, Universitätsplatz 3, 8010 Graz, Austria
Summary
Lipid-based excipients (LBEs) provide a versatile platform for pulmonary drug delivery, especially for poorly water-soluble active pharmaceutical ingredients (APIs). Their biocompatibility, solubilizing capacity, and potential for sustained release of API make them ideal for inhalation formulations. This study aimed to develop stable, spray-dried LBE-based dry powders optimized for deep-lung delivery and improved drug loading, while expanding the portfolio of LBEs for pulmonary use. Several lipids (Miglyol® 810N, Imwitor® 742, 308, and 988) and emulsifiers (Tween® 80; HLB 15.0, Gelucire® 48/16; HLB 12) were screened with a poorly water-soluble API. To facilitate spray drying of low melting point lipids, wall materials such as L-leucine and D-mannitol were incorporated into the initial formulation. High-pressure homogenization was used to prepare the aqueous nanoemulsion feed prior to spray drying. Optimization involved screening the API solubility in lipids, nanoemulsion characterization, determining optimal feed ratios for spray drying process, and assessing regulatory compliance. The spray-dried powders were evaluated for yield, particle size, and aerodynamic performance. Results identified Imwitor® 988 as the optimal lipid due to the highest API solubilization (2.87 % w/w). Nanoemulsions of Imwitor® 988 and Tween® 80 were produced with a droplet size of ~200 nm. L-leucine served effectively as a wall material, resulting in a spray-dried powder with narrow particle size distribution, fine particle fraction above 30%, and a yield exceeding 60%. This formulation enhances drug loading and exhibits favourable characteristics for pulmonary delivery, enabling incorporation of poorly soluble drugs into lipid matrices for inhalation therapy.