A Novel Gas Phase Method for the Combined Synthesis and Coating of Pharmaceutical Particles
- 178 Downloads
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.
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.
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.
Key wordsaerosol coating evaporation gas phase deposition inhalation l-leucine pharmaceutical powder production salbutamol sulfate surface modification vapor
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.
- 1.S. Budavari, M. J. O’Neil, A. Smith, and P. E. Heckelman (eds.), The Merck Index, 11th edition, 1989.Google Scholar
- 3.S. Chungi, and T. I. Iorio. Method for coating drug-containing particles and formulations and dosage units formed therefrom. WO 04/84866 (2004).Google Scholar
- 6.J. N. Israelachvili. Intermolecular & surface forces. St Edmundsbury, Suffolk, 1991.Google Scholar
- 7.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.Google Scholar
- 8.D. Lechuga-Ballesteros, and M.-C. Kuo. Dry powder compositions having improved dispersivity. WO 01/32144 (2001).Google Scholar
- 13.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).Google Scholar
- 17.X. M. Zeng, G. P. Martin, and C. Marriott. Particular interactions in dry powder formulations for inhalation. Taylor & Francis, London, 2001.Google Scholar