AAPS PharmSciTech

, Volume 14, Issue 1, pp 265–276 | Cite as

Theophylline Cocrystals Prepared by Spray Drying: Physicochemical Properties and Aerosolization Performance

  • Amjad Alhalaweh
  • Waseem Kaialy
  • Graham Buckton
  • Hardyal Gill
  • Ali Nokhodchi
  • Sitaram P. Velaga
Research Article


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.

Key words

aerodynamic diameter cocrystal spray drying surface energy theophylline 



A. Alhalaweh and S. Velaga thank the Kempe Foundation (Kempestiftelserna) for an instrumentation grant. Waseem Kaialy thanks the University of Damascus for providing PhD scholarship.

Supplementary material

12249_2012_9883_MOESM1_ESM.doc (234 kb)
ESM 1 (DOC 234 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Amjad Alhalaweh
    • 1
  • Waseem Kaialy
    • 1
    • 2
    • 3
  • Graham Buckton
    • 4
  • Hardyal Gill
    • 3
  • Ali Nokhodchi
    • 2
  • Sitaram P. Velaga
    • 1
  1. 1.Pharmaceutical Materials Research Group, Department of Health ScienceLuleå University of TechnologyLuleåSweden
  2. 2.Chemistry and Drug Delivery Group, Medway School of PharmacyUniversity of KentKentUK
  3. 3.Pharmaceutics and Pharmaceutical Technology DepartmentUniversity of DamascusDamascusSyria
  4. 4.Department of Pharmaceutics, School of PharmacyUniversity College LondonLondonUK

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