In vitro and ex vivo methods predict the enhanced lung residence time of liposomal ciprofloxacin formulations for nebulisation

Hui Xin Ong, Faiza Benaouda, Daniela Traini, David Cipolla, Igor Gonda, Mary Bebawy, Ben Forbes, Paul M. Young

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Liposomal ciprofloxacin formulations have been developed with the aim of enhancing lung residence time, thereby reducing the burden of inhaled antimicrobial therapy which requires multiple daily administration due to rapid absorptive clearance of antibiotics from the lungs. However, there is a lack of a predictive methodology available to assess controlled release inhalation delivery systems and their effect on drug disposition. In this study, three ciprofloxacin formulations were evaluated: a liposomal formulation, a solution formulation and a 1:1 combination of the two (mixture formulation). Different methodologies were utilised to study the release profiles of ciprofloxacin from these formulations: (i) membrane diffusion, (ii) air interface Calu-3 cells and (iii) isolated perfused rat lungs. The data from these models were compared to the performance of the formulations in vivo. The solution formulation provided the highest rate of absorptive transport followed by the mixture formulation, with the liposomal formulation providing substantially slower drug release. The rank order of drug release/transport from the different formulations was consistent across the in vitro andex vivo methods, and this was predictive of the profiles in vivo. The use of complimentary in vitro and ex vivo methodologies provided a robust analysis of formulation behaviour, including mechanistic insights, and predicted in vivo pharmacokinetics.
Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume86
Issue number1
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Isolated perfused lung
  • Ciprofloxacin
  • Liposomes
  • Calu-3
  • Pulmonary model
  • Transport

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