A new Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) to evaluate pulmonary drug absorption for metered dose dry powder formulations.
Absorption studies with aerosol formulation delivered by metered dose inhalers across cell- and tissue-based in vitro models of the pulmonary epithelia are not trivial due to the complexity of the processes involved: (i) aerosol generation and deposition, (ii) drug release from the carrier, and (iii) absorption across the epithelial air-blood barrier. In contrast to the intestinal mucosa, pulmonary epithelia are only covered by a thin film of lining fluid. Submersed cell culture systems would not allow to studying the deposition of aerosol particles and their effects on this delicate epithelial tissue. We developed a new Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) to mimic the inhalation of a single metered aerosol dose and its subsequent deposition on filter-grown pulmonary epithelial cell monolayers exposed to an air-liquid interface. The reproducibility of deposition of these dry powder aerosols and subsequent drug transport across Calu-3 monolayers with commercially available dry powder inhalers containing salbutamol sulphate or budesonide could be demonstrated. In the context of developing new dry powder aerosol formulations, PADDOCC appears as a useful tool, allowing reducing animal testing and faster translation into clinical trials.
Hein
Stephanie
S
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany. s.hein@mx.uni-saarland.de
Bur
Michael
M
Schaefer
Ulrich F
UF
Lehr
Claus-Michael
CM
D000042:Absorption; D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000032:analysis / Q000493:pharmacokinetics; D023401:Animal Use Alternatives; D001692:Biological Transport; D015824:Blood-Air Barrier / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000032:analysis / Q000493:pharmacokinetics*; D019819:Budesonide / Q000032:analysis / Q000493:pharmacokinetics; D018929:Cell Culture Techniques; D002460:Cell Line; D004337:Drug Carriers; D058995:Dry Powder Inhalers; D017097:Electric Impedance; D006801:Humans; D036501:Metered Dose Inhalers; D011208:Powders; D020545:Respiratory Mucosa / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility
D000336:Aerosols; D001993:Bronchodilator Agents; D004337:Drug Carriers; D011208:Powders; D019819:Budesonide; D000420:Albuterol