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Influence of Metering Chamber Volume and Water Level on the Emitted Dose of a Suspension-Based pMDI Containing Propellant 134a

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Abstract

Purpose. To determine the influence of metering chamber volume of a valve and water content of an aerosol formulation containing propellant 134a on dose delivery through the valve (DDV) and aerodynamic particle size distribution of the emitted dose.

Methods. The drug was admixed with ethanol, sonicated, and metered into cans. Valois DF10 RC valves were crimped onto the cans and propellant 134a was gassed through the valve. The DDV was determined using a dosage sampling tube. Aerodynamic particle size distributions were determined by cascade impaction. The water content was determined by Karl Fisher titration.

Results. The DDV increased linearly and the aerodynamic particle size distribution was not influenced as the metering chamber volume of the valve was increased. More drug was emitted from the valve from the initial actuations of the can than from the end. Valves with larger metering chamber volumes demonstrated less variability in DDV than those with smaller metering chamber volumes for the initial actuations. The DDV determined for actuations at the end of the can decreased as water was added extemporaneously. The mass median aerodynamic diameter (MMAD) increased as the water level was increased in the formulation. The geometric standard deviation (GSD) and percent respirable fraction (RF) were not influenced by metering chamber volume or water content.

Conclusions. The valve chosen for the development of pressurized metered dose inhaler (pMDI) formulations with propellant HFA 134a must be investigated to determine the uniformity of drug delivery. The presence of water influences the characteristics of the emitted dose.

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REFERENCES

  1. D. S. June, R. K. Schultz, and N. C. Miller. Pharm. Technol. 18:40–52, October, (1994).

    Google Scholar 

  2. M. Hill, L. Vaughan, and M. Dolovich. In R. N. Dalby, P. R. Byron, and S. J. Farr (Eds.), Respiratory Drug Delivery V, Interpharm Press, Inc., Buffalo Grove, IL, 1996, pp. 197–208.

    Google Scholar 

  3. S. J. Farr, J. A. Schuster, P. Lloyd, J. K. Okikawa, and R. M. Rubsamen. In R. N. Dalby, P. R. Byron, and S. J. Farr (Eds.), Respiratory Drug Delivery V, Interpharm Press, Inc., Buffalo Grove, IL, 1996, pp. 175–185.

    Google Scholar 

  4. S. P. Newman. In R. N. Dalby, P. R. Byron, and S. J. Farr (Eds.), Respiratory Drug Delivery V, Interpharm Press, Inc., Buffalo Grove, IL, 1996, pp. 11–18.

    Google Scholar 

  5. P. R. Byron. Pharm. Res., 11:580–584 (1994).

    Google Scholar 

  6. M. J. Molina and F. S. Rowland. Nature (Lond.), 249:810–811 (1974).

    Google Scholar 

  7. F. Moren. In F. Moren, M. B. Dolovich, M. T. Newhouse, and S.P. Newman (eds.), Aerosols in Medicine. Principles, Diagnosis and Therapy. Elsevier Science Publishers, New York, 1993, pp. 321–350.

    Google Scholar 

  8. R. N. Dalby, P. R. Byron, H. R. Shepherd, and E. Papadopoulos. Pharm. Technol. 26–33, March, (1990).

  9. I. P. Tansey. Spray Tech. Mark. 26–29, (1994).

  10. P. J. Atkins, N. P. Barker, and D. Mathisen. In A. J. Hickey (ed.), Pharmaceutical Inhalation Aerosol Technology, Marcel Dekker, Inc., New York, 1992, pp. 155–185.

    Google Scholar 

  11. Y. Kim, S. H. Atwell, and R. G. Bell. Drug Dev. Ind. Pharm. 18:2185–2195 (1992).

    Google Scholar 

  12. R. M. Evans, S. J. Farr, N. A. Armstrong, and S. M. Chatham. Pharm. Res. 8:629–635 (1991).

    Google Scholar 

  13. P. A. M. Armstrong, J. E. Carless, and R. P. Enever. J. Pharm. Pharmacol., 24:13–19 (1978).

    Google Scholar 

  14. United States Pharmacopeial Convention, Seventh Supplement to USP XXIII, USP/NF. Aerosols 601. USP, Rockville, MD, 1996, pp. 3124–3128.

    Google Scholar 

  15. R. N. Dalby and P. R. Byron. Pharm. Res. 5:36–39 (1988).

    Google Scholar 

  16. P. J. Rees, T. J. H. Clark, and F. Moren. Eur. J. Respir. Dis. 63:73–78 (1982).

    Google Scholar 

  17. W. Stahlhofen, G. Rudolf, and A. C. James. J. Aerosol Med. 2:285–308 (1989).

    Google Scholar 

  18. D. L. Swift. In A. Hicks (ed.), Inhalation Aerosols, Marcel Dekker, Inc., New York, 1996, pp. 51–81.

    Google Scholar 

  19. S. P. Newman. In K. F. Chung, and P. J. Barns (ed.), Pharmacology of the Respiratory Tract, Experimental and Clinical Research, Marcel Dekker, Inc., New York, 1993, pp. 701–728.

    Google Scholar 

  20. N. Mygind. In F. Moren, M. B. Dolovich, M. T. Newhouse, and S. P. Newman (eds.), Aerosols in Medicine. Principles, Diagnosis and Therapy. Elsevier Science Publishers, New York, 1993, pp. 1–148.

    Google Scholar 

  21. A. L. Adjei, Y. Qiu, and P. Gupta. In A. Hicks (ed.), Inhalation Aerosols, Marcel Dekker, Inc., New York, 1996, pp. 197–228.

    Google Scholar 

  22. M. J. Kontny, and G. Zografi. In H. G. Brittain (ed.), Physical Characterization of Pharmaceutical Solids, Marcel Dekker, Inc., New York, 1995, pp. 387–418.

    Google Scholar 

  23. J. M. Reynolds and D. P. McNamara. Pharm. Res. 13:809–811 (1996).

    Google Scholar 

  24. K. A. Johnson. In A. Hicks (ed.), Inhalation Aerosols, Marcel Dekker, Inc., New York, 1996, pp. 197–228.

    Google Scholar 

  25. J. Visser. Adhesion of colloidal particles. Surf. Colloid Sci. 8:3–84 (1976).

    Google Scholar 

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Authors and Affiliations

  1. Division of Pharmaceutics, College of Pharmacy, University of Texas at Austin, Austin, Texas, 78712-1074

    Robert O. Williams III, Jie Liu & John J. Koleng

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  1. Robert O. Williams III
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  2. Jie Liu
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  3. John J. Koleng
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Correspondence to Robert O. Williams III.

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Williams, R.O., Liu, J. & Koleng, J.J. Influence of Metering Chamber Volume and Water Level on the Emitted Dose of a Suspension-Based pMDI Containing Propellant 134a. Pharm Res 14, 438–443 (1997). https://doi.org/10.1023/A:1012087130114

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