title: Theophylline cocrystals prepared by spray drying: physicochemical properties and aerosolization performance.
abstract: The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials were determined. The in vitro aerosol performance of the spray-dried cocrystals, drug-alone and a drug-carrier aerosol, was assessed. The spray-dried particles had different size distributions, morphologies and surface energies. The milled samples had higher surface energy than those prepared by spray drying. Good agreement was observed between multi-stage liquid impinger and next-generation impactor in terms of assessing spray-dried THF particles. The fine particle fractions of both formulations were similar for THF, but drug-alone formulations outperformed drug-carrier formulations for the THF cocrystals. The aerosolization performance of different THF cocrystals was within the following rank order as obtained from both drug-alone and drug-carrier formulations: THF-NIC>THF-URE>THF-SAC. It was proposed that micromeritic properties dominate over particle surface energy in terms of determining the aerosol performance of THF cocrystals. Spray drying could be a potential technique for preparing cocrystals with modified physical properties.
authors.affiliation: Pharmaceutical Materials Research Group, Department of Health Science, Luleå University of Technology, Luleå, 971 87, Sweden.
authors.forename: Amjad
authors.initials: A
authors.lastname: Alhalaweh
authors.forename: Waseem
authors.initials: W
authors.lastname: Kaialy
authors.forename: Graham
authors.initials: G
authors.lastname: Buckton
authors.forename: Hardyal
authors.initials: H
authors.lastname: Gill
authors.forename: Ali
authors.initials: A
authors.lastname: Nokhodchi
authors.forename: Sitaram P
authors.initials: SP
authors.lastname: Velaga
mesh_terms: D000336:Aerosols; D002152:Calorimetry, Differential Scanning; D002849:Chromatography, Gas; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D033362:Powder Diffraction; D013806:Theophylline / Q000737:chemistry*
chemical_list: D000336:Aerosols; D013806:Theophylline