TY - JOUR
TI - Spray-dried amikacin sulphate powder for inhalation in cystic fibrosis patients: The role of ethanol in particle formation
AU - Belotti, S.
AU - Rossi, A.
AU - Colombo, P.
AU - Bettini, R.
AU - Rekkas, D.
AU - Politis, S.
AU - Colombo, G.
AU - Balducci, A.G.
AU - Buttini, F.
JO - European Journal of Pharmaceutics and Biopharmaceutics
PY - 2015
VL - 93
TODO - null
SP - 165-172
PB - Elsevier
SN - 0939-6411
TODO - 10.1016/j.ejpb.2015.03.023
TODO - alcohol;  amikacin;  aerosol;  alcohol;  amikacin;  antiinfective agent;  powder, Article;  controlled study;  cystic fibrosis;  drug solubility;  drug structure;  evaporation;  factorial design;  particle size;  particulate matter;  powder;  scanning electron microscopy;  spray drying;  temperature;  aerosol;  chemistry;  cystic fibrosis;  desiccation;  flow kinetics;  human;  inhalational drug administration;  medicinal chemistry;  microbiology;  motion;  pharmaceutics;  powder;  procedures;  Respiratory Tract Infections;  solubility;  surface property, Administration, Inhalation;  Aerosols;  Amikacin;  Anti-Bacterial Agents;  Chemistry, Pharmaceutical;  Cystic Fibrosis;  Desiccation;  Ethanol;  Humans;  Motion;  Particle Size;  Powders;  Respiratory Tract Infections;  Rheology;  Solubility;  Surface Properties;  Technology, Pharmaceutical;  Temperature
TODO - 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. © 2015 Elsevier B.V. All rights reserved.
ER -