title: Spray dried amikacin powder for inhalation in cystic fibrosis patients: a quality by design approach for product construction.
abstract: An amikacin product for convenient and compliant inhalation in cystic fibrosis patients was constructed by spray-drying in order to produce powders of pure drug having high respirability and flowability. An experimental design was applied as a statistical tool for the characterization of amikacin spray drying process, through the establishment of mathematical relationships between six Critical Quality Attributes (CQAs) of the finished product and five Critical Process Parameters (CPPs). The surface-active excipient, PEG-32 stearate, studied for particle engineering, in general did not benefit the CQAs of the spray dried powders for inhalation. The spray drying feed solution required the inclusion of 10% (v/v) ethanol in order to reach the desired aerodynamic performance of powders. All desirable function solutions indicated that the favourable concentration of amikacin in the feed solution had to be kept at 1% w/v level. It was found that when the feed rate of the sprayed solution was raised, an increase in the drying temperature to the maximum value (160 °C) was required to maintain good powder respirability. Finally, the increase in drying temperature always led to an evident increase in emitted dose (ED) without affecting the desirable fine particle dose (FPD) values. The application of the experimental design enabled us to obtain amikacin powders with both ED and FPD, well above the regulatory and scientific references. The finished product contained only the active ingredient, which keeps low the mass to inhale for dose requirement.
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. Electronic address: francesca.buttini@unipr.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Buttini
mesh_terms: D000280:Administration, Inhalation; D000583:Amikacin / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D015195:Drug Design; D005079:Excipients / Q000737:chemistry; D006801:Humans; D010316:Particle Size; D011208:Powders; D013499:Surface Properties; D013818:Thermogravimetry
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D005079:Excipients; D011208:Powders; D000583:Amikacin
keywords: Amikacin; Cystic fibrosis; Dry powder inhaler (DPI); Half-fractional factorial design; Orally inhaled drug product (OIDP)