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Production of coated and monodisperse pharmaceutical aerosols
J. Aerosol Sci., Vol. 26. Suppl 1, pp. $621-$622, 1995 Elsevier Science Ltd Printed in Great Britain 0021-8502/95 $9.50 + 0.00
~- -D e r " a m o n
PRODUCTION OF COATED AND MONODISPERSE PHARMACEUTICAL AEROSOLS S. Seemann, G.A. Ferron, R. Niel~ner, K. Willeke and J. Heyder GSF Research Center for Environment and Health Institute for Inhalation Biology 85758 Oberschleil~heim, Germany Keywords Pharmaceutical Aerosols, Aerosol Size Classifier, Coating Aerosols from jet nebulizers as used in aerosol therapy are polydisperse and hygroscopic. Particles are therefore deposited in the entire lungs and an estimation of the deposited particle mass is rather limited (Heyder, 1994). In order to improve these estimations we have developed a method to reduce the polydispersity of the aerosol and to stabilize the size of the particles. M o n o d i s p e r s e aerosol A new aerosol size classifier (ASC) was developed. A polydisperse aerosol generated by jet nebulization and clean air enter the ASC (fig. 1). The separation unit consits of three ducts for small (< 1,4pm), medium and large (> 2,1pm) particles. The medium particles are suitable for aerosol therapy. Their size distribution is adjustable within a range of 1.4-2.11Jm NMAD and a GSD of 1.2.
small particles
poly-
disperse aerosol
medium particles large particles
monodisperse aerosol
clean air
Figure I: The aersol size classifier Coating The monodisperse particles are transported to a thermostated ring-gap mixing nozzle (Niel~ner, 1984) for coating them with a thin layer of stearic acid by condensation. The stability of the coated particles is determined by exposing them to dry or humid air. At relative humidities (rh) between 60 and 80% particle size distributions are measured with a light scattering particle detector.(LAS-X, PMS, Boulder).
Validation Monodisperse particles with a NMAD of 1,91Jm separated from polydisperse NaCI droplets are exposed to dry air to determine the stability of the coating. Fig. 2 shows a typical exS621
$622
S. SEEMANNet al.
ample of the number concentration of coated and uncoated particles, fig. 3 the number concentration of coated particles after different time intervals. 400
280 ,
350 300 rl uncoated 160 t
i
X
'=1
250
coated
200 150
8o ~
I
100
50 ,
0,1
,
0
10
,
0,1
I particle diameter Otm)
particle diameter (pm)
Figure 2: Particle size distribution of coated and uncoated aqueous NaCI particles at 75.4% rh
10
Figure 3: Temporal variation of size distributions of coated NaCI particles at 76.1% rh
The coated particles show a strong retardation of the evaporation (fig. 2) and the organic coating is stable for 10 seconds (fig. 3). Deposition of uncoated fluorescent Bricanyl/disodium fluorescein (DF) particles in a cylindrical tube increases from 1.3% to 7.3% (fig. 4 ) with increasing humidities because of hygroscopic particle growth. However, coating these particles with stearic acid prevents hygroscopic growth so that their deposition is independent of humidity (fig. 5). 10
16
9
I4
=suits tits
8 12
experimental results
7
~:~:theoretical ~ results
10 8
4
6
3 4
2
ill
1 0
72,5
91,1
96,1 relative humidity (%)
2 0
99,8
Figure 4: Deposition of uncoated Bricanyl/DF particles in a cylindrical tube at different relative humidities
72,8
91,9
98,3
99,6
relative humidity (%)
Figure 5: Deposition of coated aqueous Bdcanyl/DF particles in a cylindrical tube at different relative humidities
References Heyder, J. (1994). New trends in aerosol therapy: the physicist's view. Eur. Respir. Rev., 18, 104-105. Niel~ner, R. (1984). Coated Particles: Preliminary results of laboratory studies on interaction of ammonia with coated sulfuric acid droplets or hydrogensulfate particles. Sci. Total Environment, 36, 353-362.
~- -D e r " a m o n
PRODUCTION OF COATED AND MONODISPERSE PHARMACEUTICAL AEROSOLS S. Seemann, G.A. Ferron, R. Niel~ner, K. Willeke and J. Heyder GSF Research Center for Environment and Health Institute for Inhalation Biology 85758 Oberschleil~heim, Germany Keywords Pharmaceutical Aerosols, Aerosol Size Classifier, Coating Aerosols from jet nebulizers as used in aerosol therapy are polydisperse and hygroscopic. Particles are therefore deposited in the entire lungs and an estimation of the deposited particle mass is rather limited (Heyder, 1994). In order to improve these estimations we have developed a method to reduce the polydispersity of the aerosol and to stabilize the size of the particles. M o n o d i s p e r s e aerosol A new aerosol size classifier (ASC) was developed. A polydisperse aerosol generated by jet nebulization and clean air enter the ASC (fig. 1). The separation unit consits of three ducts for small (< 1,4pm), medium and large (> 2,1pm) particles. The medium particles are suitable for aerosol therapy. Their size distribution is adjustable within a range of 1.4-2.11Jm NMAD and a GSD of 1.2.
small particles
poly-
disperse aerosol
medium particles large particles
monodisperse aerosol
clean air
Figure I: The aersol size classifier Coating The monodisperse particles are transported to a thermostated ring-gap mixing nozzle (Niel~ner, 1984) for coating them with a thin layer of stearic acid by condensation. The stability of the coated particles is determined by exposing them to dry or humid air. At relative humidities (rh) between 60 and 80% particle size distributions are measured with a light scattering particle detector.(LAS-X, PMS, Boulder).
Validation Monodisperse particles with a NMAD of 1,91Jm separated from polydisperse NaCI droplets are exposed to dry air to determine the stability of the coating. Fig. 2 shows a typical exS621
$622
S. SEEMANNet al.
ample of the number concentration of coated and uncoated particles, fig. 3 the number concentration of coated particles after different time intervals. 400
280 ,
350 300 rl uncoated 160 t
i
X
'=1
250
coated
200 150
8o ~
I
100
50 ,
0,1
,
0
10
,
0,1
I particle diameter Otm)
particle diameter (pm)
Figure 2: Particle size distribution of coated and uncoated aqueous NaCI particles at 75.4% rh
10
Figure 3: Temporal variation of size distributions of coated NaCI particles at 76.1% rh
The coated particles show a strong retardation of the evaporation (fig. 2) and the organic coating is stable for 10 seconds (fig. 3). Deposition of uncoated fluorescent Bricanyl/disodium fluorescein (DF) particles in a cylindrical tube increases from 1.3% to 7.3% (fig. 4 ) with increasing humidities because of hygroscopic particle growth. However, coating these particles with stearic acid prevents hygroscopic growth so that their deposition is independent of humidity (fig. 5). 10
16
9
I4
=suits tits
8 12
experimental results
7
~:~:theoretical ~ results
10 8
4
6
3 4
2
ill
1 0
72,5
91,1
96,1 relative humidity (%)
2 0
99,8
Figure 4: Deposition of uncoated Bricanyl/DF particles in a cylindrical tube at different relative humidities
72,8
91,9
98,3
99,6
relative humidity (%)
Figure 5: Deposition of coated aqueous Bdcanyl/DF particles in a cylindrical tube at different relative humidities
References Heyder, J. (1994). New trends in aerosol therapy: the physicist's view. Eur. Respir. Rev., 18, 104-105. Niel~ner, R. (1984). Coated Particles: Preliminary results of laboratory studies on interaction of ammonia with coated sulfuric acid droplets or hydrogensulfate particles. Sci. Total Environment, 36, 353-362.