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

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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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Pharmaceutical Materials Research Group, Department of Health Science, Luleå University of Technology, Luleå, 971 87, Sweden

    Amjad Alhalaweh, Waseem Kaialy & Sitaram P. Velaga

  2. Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB, Kent, UK

    Waseem Kaialy & Ali Nokhodchi

  3. Pharmaceutics and Pharmaceutical Technology Department, University of Damascus, Damascus, Syria

    Waseem Kaialy & Hardyal Gill

  4. Department of Pharmaceutics, School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK

    Graham Buckton

Authors
  1. Amjad Alhalaweh
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  2. Waseem Kaialy
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  3. Graham Buckton
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  4. Hardyal Gill
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  6. Sitaram P. Velaga
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Correspondence to Sitaram P. Velaga.

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Alhalaweh, A., Kaialy, W., Buckton, G. et al. Theophylline Cocrystals Prepared by Spray Drying: Physicochemical Properties and Aerosolization Performance. AAPS PharmSciTech 14, 265–276 (2013). https://doi.org/10.1208/s12249-012-9883-3

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  • DOI: https://doi.org/10.1208/s12249-012-9883-3

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