Measurement of the hygroscopicity of pharmaceutical aerosols in situ

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J. Aerosol Sci., Vol. 26. Suppl 1, pp. $537-$538, 1995 Elsevier Science Ltd Printed in Great Britain 0021-8502/95 $9.50 + 0.00

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MEASUREMENT OF THE HYGROSCOPICITY OF PHARMACEUTICAL AEROSOLS in situ S. Seemann, B. Busch, G. A. Ferron, A. Silberg and J. Heyder GSF Research Center for Environment end Health Institute for Inhalation Biology 85758 Oberschlei~heim, Germany Keywords Pharmaceuticals, Hygroscopicity, Differential Mobility Analyser INTRODUCTION The deposition pattern of particles in the human lung depends strongly on the particle diameter. Hydrophilic particles grow considerably at the high relative humidity of 99,5% in the respiratory tract. The hygroscopicity of pharmaceutical aerosols is normaly determined by measuring the freezing point depression of the bulk solution. These measurements are normalized for a 0.9% NaCI solution by weight, having a freezing point depression of 0.52°C. Results are available for many different salts but only for few drugs (Budavari, 1989). In practice materials like NaCI, lactose or citric acid have been added to drugs to improve their properties. These additives influence the hygroscopicity of the aerosol. In order to study the hygroscopic properties of the drug aerosols in situ a tandem differential mobility analyser is used (Busch, 1994). METHOD A tandem differential mobility analyser (TDMA) consists of two differential mobility analysers (DMA). The first DMA selects a monodisperse fraction from a dry polydisperse drug aerosol. A humidifier adjusted to a preset relative humidity moistens the drug particles and the second DMA determines the size of the grown drug particles. The measured growth factors are compared with theoretically calculated values (Ferron, 1993). The increased mass of the droplets at a relative humidity of 99,5% in the human lungs can be estimated, assuming that the dissociation parameter of the drug is independent of the concentration. RESULTS and DISCUSSION Measurements have been performed for pure substances (NaCI, terbutaline sulphate and cromoglycin disodium) (tab. 1) and for related drugs (tab. 2). The theoretical and experimental values for NaCI and terbutaline sulfate show good agreement. For cromoglycin disodium in tab. 1 and drugs in tab. 2 theoretical growth factors can't be calculated because their physical properties like density and isosmotic concentration are not known. $537

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Table 1. Hygroscopic growth factors of dry 0.1651Jm particles (pure substances). Composition of dry particles

Relative humidity

Experiment

Theory

NaCI

0.969

3.19

3.29

,,

0.955

2.81

2.94

,,

0.931

2.64

2.59

,,

0.891

2.36

2.26

Terbutaline sulphate

0.971

1.33

1.44

,,

0.921

1.15

1.24

,,

0.880

1.13

1.16

Cromoglycin disodium

0.973

1.28

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Table 2. Hygroscopic growth factors of dry 0.165pm particles (drugs). Composition of dry particles

Relative humidity

Experiment

Aerodur (Pharma-stern)

0.980

1.37

Bricanyl (Pharma-stern)

0.980

2.44

Cromolind (Lindopharm)

0.980

1.48

Intal powder (Fisons)

0.974

1.30

Intal composit (Fisons)

0.974

1.30

The results of table 1 and 2 show that the TDMA method is suitable to determine the hygroscopic properties of drug aerosol particles in situ. REFERENCES Budavari, S. (1989) The Merck Index, Merck & Co., Rahway, N. J. Busch, B., Ferron, G.A., Karg, E., Silberg, A., Heyder, J. (1994) The growth of atmospheric particles in moist air. J. Aerosol Sci., 25, $143-$144. Ferron, G. A., Karg, E., Peter, J. L. (1993) Estimation of deposition of polydisperse hygroscopic aerosols in the human respiratory tract. J. Aerosol Sci., 24, 655-670.