title: Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air-Liquid Interface Cultured Cell Layer.
abstract: Most safety evaluations of dry powder inhalers (DPIs) using cultured cells have been performed with dry powder formulations dissolved in a medium. However, this method is not considered to be suitable to evaluate the safety of inhaled dry powder formulations correctly since it cannot reflect the actual phenomenon on the respiratory epithelial surface. In this study, we established a novel in-vitro safety evaluation system suitable for DPIs by combining an air-liquid interface cultured cell layer and a device for dispersing dry powders, and evaluated the safety of candidate excipients of dry powders for inhalation. The safety of excipients (sugars, amino acids, cyclodextrins, and positive controls) in solutions was compared using submerged cell culture systems with a conventional 96-well plate and Transwell(®). The sensitivity of the cells grown in Transwell(®) was lower than that of those grown in the 96-well plate. Dry powders were prepared by spray-drying and we evaluated their safety with a novel in-vitro safety evaluation system using an air-liquid interface cultured cell layer. Dry powders decreased the cell viability with doses more than solutions. On the other hand, dissolving the dry powders attenuated their cytotoxicity. This suggested that the novel in-vitro safety evaluation system would be suitable to evaluate the safety of DPIs with high sensitivity.
authors.affiliation: Faculty of Pharmacy, Meijo University.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Asai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Okuda
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sugiura
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000388:Air; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D058995:Dry Powder Inhalers; D005079:Excipients / Q000494:pharmacology*; D006801:Humans; D010316:Particle Size; D011208:Powders
chemical_list: D005079:Excipients; D011208:Powders