Thermal ink-jet spray freeze-drying for preparation of excipient-free salbutamol sulphate for inhalation

• Published in: European journal of pharmaceutics and biopharmaceutics 2012, Vol.80 (1), p.149-155
• Main Authors: Mueannoom, Wunlapa, Srisongphan, Amon, Taylor, Kevin M.G., Hauschild, Stephan, Gaisford, Simon
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosols - chemistry; Albuterol - administration & dosage; Albuterol - chemistry; Biological and medical sciences; Chemistry, Pharmaceutical - instrumentation; Chemistry, Pharmaceutical - methods; Drug Stability; Dry powder inhaler; Excipient-free; Excipients - chemistry; Freeze Drying - methods; General pharmacology; Ink; Medical sciences; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Porosity; Porous particles; Salbutamol sulphate; Solutions - chemistry; Spray freeze-drying; Thermal ink-jet
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.09.016

Salbutamol sulphate particles prepared with thermal ink-jetting spray freeze-drying (TIJ-SFD), left, and spray drying, right. The use of thermal ink-jet spray freeze-drying (TIJ-SFD) to engineer inhalable, excipient-free salbutamol sulphate (SS) particles was assessed. A modified Hewlett-Packard printer was used to atomise aqueous SS solutions into liquid nitrogen. The frozen droplets were freeze-dried. It was found that TIJ-SFD could process SS solutions up to 15% w/v; the porous particles produced had a physical diameter of ca. 35 μm. Next generation impactor (NGI) analysis indicated that the particles had a smaller aerodynamic size (MMAD ranging from 6 to 8.7 μm). Particles prepared from the lowest concentration SS solution were too fragile to withstand aerosolisation, but the 5% w/v solution yielded particles having the best combination of strength and aerodynamic properties. Comparison with a commercial SS formulation (Cyclocap®) showed that the SFD preparation had an almost equivalent FPF 6.4μm when analysed with a twin-stage impinger (TSI; 24.0 ± 1.2% and 26.4 ± 2.2%, respectively) and good performance when analysed with NGI (FPF 4.46μm:16.5 ± 2.0 and 27.7 ± 1.7, respectively). TIJ-SFD appears to be an excellent method to prepare inhalable particles. It is scalable yet allows assessment of the viability of the pulmonary route early in the development since it can be used with very small volumes (