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

• Published in: AAPS PharmSciTech 2013-03, Vol.14 (1), p.265-276
• Main Authors: Alhalaweh, Amjad, Kaialy, Waseem, Buckton, Graham, Gill, Hardyal, Nokhodchi, Ali, Velaga, Sitaram P.
• Format: Article
• Language: English
• Subjects: Aerosols; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calorimetry, Differential Scanning; Chromatography, Gas; Health Science; Hälsovetenskap; Microscopy, Electron, Scanning; Particle Size; Pharmacology/Toxicology; Pharmacy; Powder Diffraction; Research Article; Theophylline - chemistry
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-012-9883-3

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.