Abstract
Purpose
A novel aerosol flow reactor method for the combined gas phase synthesis and coating of particles for drug delivery has been developed.
Materials and Methods
As an example, micron-sized salbutamol sulfate particles were produced via droplet-to-particle conversion and in-situ coated by the physical vapor deposition (PVD) of l-leucine vapor.
Results
During the deposition, l-leucine vapor crystallized on the surfaces of amorphous salbutamol particles. The size of l-leucine crystallites increased with increasing vapor concentration of l-leucine. The salbutamol particles with rough l-leucine surfaces exhibited good flowability enabling to them to be dispersed into air flow without the delivery aid of coarse lactose carriers.
Conclusions
The fraction of particles smaller than 5 micrometers varied between 0.35 and 0.48 when dispersed into 60 l/min air flow having a jet Reynolds number of 30700. When the coated fine particles were blended with lactose carriers, the fine particle fraction was as high as 90%. The l-leucine coating also improved the stability of salbutamol particles when stored at 45% relative humidity atmosphere.
This is a preview of subscription content, log in via an institution to check access.
References
S. Budavari, M. J. O’Neil, A. Smith, and P. E. Heckelman (eds.), The Merck Index, 11th edition, 1989.
N. Y. K. Chew, B. Y. Shekunov, H. H. Y. Tong, A. H. L. Chow, C. Savage, J. Wu, and H.-K. Chan. Effect of amino acids on the dispersion of disodium cromoglycate powders. J. Pharm. Sci. 94:2289–2300 (2005).
S. Chungi, and T. I. Iorio. Method for coating drug-containing particles and formulations and dosage units formed therefrom. WO 04/84866 (2004).
H. Eerikäinen, W. Watanabe, E. I. Kauppinen, and P. P. Ahonen. Aerosol flow reactor method for synthesis of drug nanoparticles. Eur. J. Pharm. Biopharm 55:357–360 (2003).
R. Hillamo, and E. I. Kauppinen. On the performance of the Berner low pressure impactor. Aerosol Sci. Tech 14:33–47 (1991).
J. N. Israelachvili. Intermolecular & surface forces. St Edmundsbury, Suffolk, 1991.
J. A. Kurkela, D. P. Brown, J. Raula, and E. I. Kauppinen. Studies on powder deagglomeration into turbulent jet flow. In C. Kanaoka, H. Makino, and H. Kamiya (eds.), Advanced Gas Cleaning Technology, Jugei Shobo, Tokyo, 2005pp. 249–255.
D. Lechuga-Ballesteros, and M.-C. Kuo. Dry powder compositions having improved dispersivity. WO 01/32144 (2001).
Q. Li, V. Rudolph, and W. Peukert. London-van der Waals adhesiveness of rough particles. Powder Technol 161:248–255 (2006).
P. Lucas, K. Anderson, U. J. Potter, and J. N. Staniforth. Enhancement of small particle size dry powder aerosol formulations using an ultra low density additive. Pharm. Res 16:1643–1647 (1999).
F. Podczeck. The influence of particle size distribution and surface roughness of carrier particles on the in vitro properties of dry powder inhalations. Aerosol Sci. Technol 21:301–321 (1999).
J. Raula, H. Eerikäinen, and E. I. Kauppinen. Influence of the solvent composition on the morphology of polymer drug composite nanoparticles. Int. J. Pharm 284:13–21 (2004).
J. N. Staniforth, and D. A. V. Morton. Magnesium stearate, a phospholipid, or an amino acid in preparation of pharmaceutical particles for inhalation. WO 02/43700 (2002).
S. Watano, H. Nakamura, K. Hamada, Y. Wakamatsu, Y. Tanabe, R. N. Dave, and R. Pfeffer. Fine particle coating by a novel rotating fluidized bed coater. Powder Technol 141:172–176 (2004).
B. Yue, J. Yang, Y. Wang, C.-Y. Huang, R. Dave, and R. Pfeffer. Particle encapsulation with polymers via in situ polymerization in supercritical CO2. Powder Technol 146:32–45 (2004).
X. M. Zeng, G. P. Martin, S.-K. Tee, and C. Marriott. The role of fine particle lactose on the dispersion and deagglomeration of salbutamol sulfate in an air stream in vitro. Int. J. Pharm 176:99–110 (1998).
X. M. Zeng, G. P. Martin, and C. Marriott. Particular interactions in dry powder formulations for inhalation. Taylor & Francis, London, 2001.
Y. Zhu, and K. W. Lee. Experimental study on small cyclones operating at high flow rates. J. Aerosol Sci 30:1303–1315 (1999).
Acknowledgements
Financial support from the Finnish Academy is gratefully acknowledged. We thank Dr. Hua Jiang for the TEM analysis and Mr. Raoul Järvinen for assistance in building the experimental set-up.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Raula, J., Lähde, A. & Kauppinen, E.I. A Novel Gas Phase Method for the Combined Synthesis and Coating of Pharmaceutical Particles. Pharm Res 25, 242–245 (2008). https://doi.org/10.1007/s11095-007-9464-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-007-9464-4