Characterization of nebulized buparvaquone nanosuspensions—effect of nebulization technology

The poorly soluble drug buparvaquone is proposed as an alternative treatment of Pneumocystis carinii pneumonia (PCP) lung infections. Physically stable nanosuspensions were formulated in order to deliver the drug at the site of infection using nebulization. The aerosolization characteristics of two buparvaquone nanosuspensions were determined with commercial jet and ultrasonic nebulizer devices. Aerosol droplet size distribution was determined with laser diffractometry (LD). Nebulization of the nanosuspensions and dispersion media surfactant solutions produced aerosol droplets diameters in the range from 3 to 5 μm for Respi-jet Kendall, Pari Turbo Boy system and Multisonic nebulizers and particles around 9–10 μm with Omron U1. Fractions of the nanosuspensions from the nebulizer reservoir and of aerosol produced were collected to investigate changes in the size of the drug nanocrystals influenced by the nebulization technology. Comparisons were performed measuring the drug nanocrystals with photon correlation spectroscopy (PCS) and LD of the samples. Drug particle aggregates were detected in the fractions of aerosol collected from jet nebulizers. Nebulizer technology (jet vs. ultrasonic) showed influence on the stability of the drug particle size distribution of buparvaquone nanocrystals during the nebulization time evaluated.

[1]  T. O'Riordan.  Formulations and nebulizer performance. , 2002, Respiratory care.

[2]  S. J. Levine.  Pneumocystis carinii. , 1996, Clinics in chest medicine.

[3]  J. Montaner,et al.  Atovaquone suspension compared with aerosolized pentamidine for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected subjects intolerant of trimethoprim or sulfonamides. , 1999, The Journal of infectious diseases.

[4]  J. Montaner,et al.  Atovaquone suspension for treatment of Pneumocystis carinii pneumonia in HIV-infected patients , 2001, AIDS.

[5]  R. Müller,et al.  Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. , 2001, Advanced drug delivery reviews.

[6]  A. Wakefield.  Pneumocystis carinii. , 2002, British medical bulletin.

[7]  H. Bosch,et al.  An in-vitro assessment of a NanoCrystal beclomethasone dipropionate colloidal dispersion via ultrasonic nebulization. , 1999, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[8]  M. Dahlbäck.  Behavior of nebulizing solutions and suspensions. , 1994, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[9]  H. Masur,et al.  Adverse events associated with trimethoprim-sulfamethoxazole and atovaquone during the treatment of AIDS-related Pneumocystis carinii pneumonia. , 1995, The Journal of infectious diseases.

[10]  J. Phair,et al.  Predictors for failure of Pneumocystis carinii pneumonia prophylaxis. Multicenter AIDS Cohort Study. , 1995, JAMA.

[11]  I. Gonda.  A semi‐empirical model of aerosol deposition in the human respiratory tract for mouth inhalation , 1981, The Journal of pharmacy and pharmacology.

[12]  K.M.G. Taylor,et al.  Jet nebulisers for pulmonary drug delivery , 1996 .

[13]  O. Kayser,et al.  Pneumocystis carinii Synthesizes Four Ubiquinone Homplogs: Inhibition by Atovaquone and Bupravaquone but not by Stigmatellin , 2001, The Journal of eukaryotic microbiology.

[14]  H. Steckel,et al.  Factors affecting aerosol performance during nebulization with jet and ultrasonic nebulizers. , 2003, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[15]  R. Müller,et al.  Production and Characterization of a Budesonide Nanosuspension for Pulmonary Administration , 2002, Pharmaceutical Research.

[16]  W. El-Sadr,et al.  Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community Program for Clinical Research on AIDS and the AIDS Clinical Trials Group. , 1998, The New England journal of medicine.

[17]  K. Taylor,et al.  Nebulization of Fluids of Different Physicochemical Properties with Air-Jet and Ultrasonic Nebulizers , 1995, Pharmaceutical Research.

[18]  C O'Callaghan,et al.  The science of nebulised drug delivery , 1997, Thorax.

[19]  J. Falloon,et al.  Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. , 1993, The New England journal of medicine.

[20]  J. Margolick,et al.  Predictors for Failure of Pneumocystis carinii Pneumonia Prophylaxis , 1995 .