Issue link: https://www.e-digitaleditions.com/i/1481142
Inhalation OctOber 2022 11 products can be designed to prevent exhalation of cytotoxic powders [6]. In addition to the case studies discussed in detail below, here are a few studies that demonstrate dry powder formulations for local treatment of lung cancer: • Camptothecin, a naturally occurring topoisomer- ase I inhibitor, was formulated as a dry powder by spray drying and delivered to rats by inhalation. Drug levels in lung tissue were ten-fold higher for the inhaled treatment compared with the same dose delivered intravenously [7]. • Topotecan, approved for IV administration for multiple cancer types, was also employed as a spray-dried powder for inhalation. Delivery by the inhalation route substantially improved topote- can's efficacy in a rat model of NSCLC, both in local and distant tumors [8, 9]. • 5-azacytidine is a demethylation agent of interest for lung cancer treatment, which has poor expo- sure in lung tissue when delivered intravenously. Kuehl, et al. demonstrated that a dry powder for- mulation delivered by inhalation had superior pharmacokinetics (PK) in rats compared with IV administration. In addition, it reduced tumor bur- den in an orthotopic rat model of NSCLC [10]. Inhaled 5-azacytidine also was well-tolerated by NSCLC patients in a Phase I clinical study using a nebulized liquid formulation [11]. neering needs of an inhaled product into a single process step. In spray drying, the API and excipi- ents are co-dissolved into a volatile solvent. Liquid is pumped through an atomizer, where it is broken up into small droplets. In the drying chamber, the solvent is rapidly removed from the droplets via a heated drying gas, producing a dry powder prod- uct. To achieve the target particle size necessary for delivery to the deep lung, droplet size, solution com- position and drying kinetics are important process parameters. As discussed in the case studies pre- sented here, spray drying can be applied to a wide range of APIs, including small molecules and large biotherapeutics, such as monoclonal antibodies, oli- gonucleotides and other proteins. Precedented in the literature Inhaled chemotherapy for treatment of lung cancer is precedented in the literature and was reviewed recently by Rosière. et al. [6]. A primary concern for inhaled chemotherapy delivered by nebulizer is contamination of the surrounding environment with cytotoxic compounds. Burdensome infra- structure such as containment tents, filter appara- tuses or mouth-only devices have been proposed to protect healthcare workers administering these treatments . ese challenges can be largely amelio- rated by the use of a dry powder inhaler, in which