title: Spray-dried amikacin sulphate powder for inhalation in cystic fibrosis patients: The role of ethanol in particle formation.
abstract: A Central Composite Design (CCD) was applied in order to identify positive combinations of the production parameters of amikacin sulphate spray-dried powders for inhalation, with the intent to expand the experimental space defined in a previous half-fractional factorial design. Three factors, namely drying temperature, feed rate and ethanol proportion, have been selected out of the initial five. In addition, the levels of these factors were increased from two to three and their effect on amikacin respirability was evaluated. In particular, focus was given on the role of ethanol presence on the formation of the microparticles for inhalation. The overall outcome of the CCD was that amikacin respirability was not substantially improved, as the optimum region coincided with areas already explored with the fractional factorial design. However, expanding the design space towards smaller ethanol levels, including its complete absence, revealed the crucial role of this solvent on the morphology of the produced particles. Peclet number and drug solubility in the spraying solution helped to understand the formation mechanism of these amikacin sulphate spray-dried particles.
authors.affiliation: Department of Pharmacy, University of Parma, Viale delle Scienze 27/A, Parma 43124, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Belotti
authors.affiliation: Department of Pharmacy, University of Parma, Viale delle Scienze 27/A, Parma 43124, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Pharmacy, University of Parma, Viale delle Scienze 27/A, Parma 43124, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Colombo
authors.affiliation: Department of Pharmacy, University of Parma, Viale delle Scienze 27/A, Parma 43124, Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Bettini
authors.affiliation: School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Rekkas
authors.affiliation: School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Politis
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, via Fossato di Mortara 17/19, Ferrara 44121, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Colombo
authors.affiliation: Interdepartmental Center, Biopharmanet-TEC, University of Parma, Viale delle Scienze 27/A, Parma 43124, Italy.
authors.forename: Anna Giulia
authors.initials: AG
authors.lastname: Balducci
authors.affiliation: Department of Pharmacy, University of Parma, Viale delle Scienze 27/A, Parma 43124, Italy; Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, SE19NH London, United Kingdom. Electronic address: francesca.buttini@unipr.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Buttini
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000583:Amikacin / Q000008:administration & dosage / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000382:microbiology; D003890:Desiccation; D000431:Ethanol / Q000737:chemistry*; D006801:Humans; D009038:Motion; D010316:Particle Size; D011208:Powders; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D012212:Rheology; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D011208:Powders; D000431:Ethanol; D000583:Amikacin
keywords: Amikacin sulphate; Amikacin sulphate (PubChem CID: 45357036); Cystic fibrosis; Dry powder inhaler; Microparticles; Peclet number