Characterisation of a Carrier-Free Dry Powder Aerosol Formulation Using Inertial Impaction and Laser Diffraction
The purpose of the study was to examine the suitability of using laser diffraction to measure the fine particle fraction (FPF) of drugs emitted from carrier-free dry powder aerosol formulations.
Materials and Methods
Particle size distribution of terbutaline sulphate from Bricanyl™ Turbohaler™, which contained loose agglomerates of drug particles only, was measured separately by laser diffraction apparatus equipped with a metal throat and a twin-stage, multi-stage liquid impingers, or Andersen cascade impactor at flow rates ranging from 28.3 to 100 l min−1. In-line measurements were then conducted which allowed the same aerosolised particles to be measured first by laser diffraction then captured by an impactor or impinger for subsequent chemical analysis.
A significant linear correlation (p < 0.001, R 2 = 0.96, ANOVA) existed between the results obtained from two techniques when measurements were conducted independently. There was little difference in FPFs measured by inertial impaction and laser diffraction at the same flow rate. When in-line measurements were conducted, the FPFs measured by inertial impaction were approximately 0.7–0.9 times the aerosol FPFs measured by laser diffraction. This linear relationship was statistically significant and had a statistically insignificant y-intercept, regardless of inhaler batches, impinger types and measuring position of the laser beam.
Laser diffraction could prove to be a reliable technique for development, evaluation and quality control of carrier-free, dry powder aerosol formulations.
Key wordsBricanyl™ Turbohaler™ dry powder aerosols formulations inertial impaction laser diffraction particle size distribution
- 3.B. Olsson, H. Jægfeldt, K. Hed, and H. Ludback. Correlation between laser scattering and inertial impaction for the particle distribution charactersation of Bricanyl Turbohaler. J. Aerosol Sci. 19:1107–1111 (1988).Google Scholar
- 7.X. M. Zeng, H. B. MacRitchie, C. Marriott, and G. P. Martin. Correlation between inertial impaction and laser diffraction sizing data for aerosolized carrier-based dry powder formulations. Submitted for publication.Google Scholar
- 9.T. T. Yang and D. Kenyon. Use of an agglomerate formulation in a new multidose dry powder inhaler. In R. N. Dalby, P. R. Byron, and S. J. Farr (eds.), Respiratory Drug Delivery VII, Serentec, Raleigh, North Carolina, 2000, pp. 503–505.Google Scholar
- 10.S. White and N. Harper. Exubera®: development of a novel technology solution for pulmonary delivery of insulin. In Proceedings of drug delivery to the lung 15, The Aerosol Society, London, 2004, pp. 89–92.Google Scholar
- 11.Handbook of Pharmaceutical Excipients, 4th ed., American Pharmaceutical Association, Washington, District of Columbia, 2003.Google Scholar
- 12.British Pharmacopoeia. Aerodynamic Assessment of Fine Particles. HMSO, London, Appendix XII F, 2000, A194–A200.Google Scholar
- 13.H. Jægfeldt, J. A. R. Andersson, E. Trofast, and K. I. L. Wetterlin. Particle size distribution from different modifications of Turbohaler™. In S. P. Newman, F. Moren, and G. K. Compton (eds.), A New Concept in Inhalation Therapy, Medicom, Netherlands, 1987, pp. 90–99.Google Scholar
- 14.A. H. de Boer, D. Gjaltema, and P. Hageforn. Inhalation characteristics and their effect on in vitro drug delivery from dry powder inhalers. Part 2: Effect of peak flow rate (PIFR) and inspiration time on the in vitro drug release from 3 types of commercial dry powder inhalers. Int. J. Pharm. 138:45–56 (1996).CrossRefGoogle Scholar
- 17.E. D. Hirleman. Particle sizing by non-imaging techniques. In J. M. Tishkoff, R. D. Ingebo, and J. B. Kennedy (eds.), Liquid Particle Size Measurement Techniques ASTM STP 848, American Society for Testing and Materials, Philadelphia, 1984, pp. 35–60.Google Scholar
- 18.H. C. Van de Hulst. Light Scattering by Small Particles. Dover, New York, 1981.Google Scholar
- 19.P. Kippax. Appraisal of the laser diffraction particle-sizing technique. Pharm. Technol. 88–96 (2005).Google Scholar
- 21.J. Swithenbank, J. M. Beer, D. S. Taylor, and G. C. MeCreath. A laser diagnostic technique for the measurement of droplet and particle size distribution. Prog. Aeronaut. 53:421 (1977).Google Scholar