Formulation and Characterization of Lipid-Coated Tobramycin Particles for Dry Powder Inhalation


This study was conducted to develop and evaluate the physicochemical and aerodynamic characteristics of lipid-coated dry powder formulations presenting particularly high lung deposition.


Lipid-coated particles were prepared by spray-drying suspensions with different concentrations of tobramycin and lipids. The solid-state properties of the formulations, including particle size and morphology, were assessed by scanning electron microscopy and laser diffraction. Aerosol performance was studied by dispersing the powders into a Multistage Liquid Impinger and determining drug deposition by high-performance liquid chromatography.


Particle size distributions of the formulations were unimodal, narrow with more than 90% of the particles having a diameter of less than 2.8 μm. All powder formulations exhibited mass median diameters of less than 1.3 and 3.2 μm, as determined by two different laser diffraction methods, the Malvern's Mastersizer® and Spraytec®, respectively. The fine particle fraction varied within a range of 50.5 and 68.3%.


Lipid coating of tobramycin formulations resulted in a reduced agglomeration tendency and in high fine particle fraction values, thus improving drug deposition. The very low excipients content (about 5% m/m) of these formulations offers the benefit of delivering particularly huge concentrations of antibiotic directly to the site of infection, while minimizing systemic exposure, and may provide a valuable alternative treatment of cystic fibrosis.

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  1. 1.

    R. Moss (2002) ArticleTitleLong-term benefits of inhaled tobramycin in adolescent patients with cystic fibrosis Chest 121 55–63 Occurrence Handle11796432 Occurrence Handle1:CAS:528:DC%2BD38Xht1yltbs%3D Occurrence Handle10.1378/chest.121.1.55

    PubMed  CAS  Article  Google Scholar 

  2. 2.

    F. S. Collins (1992) ArticleTitleCystic fibrosis: molecular biology and therapeutic implications Science 256 774–779 Occurrence Handle1375392 Occurrence Handle1:CAS:528:DyaK38XktVGit7c%3D

    PubMed  CAS  Google Scholar 

  3. 3.

    R. Moss (1995) ArticleTitleCystic fibrosis: pathogenesis, pulmonary infection, and treatment Clin. Infect. Dis. 21 839–849 Occurrence Handle8645828 Occurrence Handle1:CAS:528:DyaK2MXpsl2jt78%3D

    PubMed  CAS  Google Scholar 

  4. 4.

    M. E. Hodson C. G. Gallagher J. R. W. Govan (2002) ArticleTitleA randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis Eur. Respir. J. 20 658–664 Occurrence Handle12358344 Occurrence Handle1:CAS:528:DC%2BD38Xotl2is7c%3D Occurrence Handle10.1183/09031936.02.00248102

    PubMed  CAS  Article  Google Scholar 

  5. 5.

    C. Koch N. Hoiby (1993) ArticleTitlePathogenesis of cystic fibrosis Lancet 341 1065–1069 Occurrence Handle7682274 Occurrence Handle1:STN:280:ByyB38rnt1U%3D Occurrence Handle10.1016/0140-6736(93)92422-P

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    D. E. Geller W. H. Pitlick P. A. Nardella W. G. Tracewell B. W. Ramsey (2002) ArticleTitlePharmacokinetics and bioavailability of aerolized tobramycin in cystic fibrosis Chest 122 219–226 Occurrence Handle12114362 Occurrence Handle1:CAS:528:DC%2BD38XmtF2is7s%3D Occurrence Handle10.1378/chest.122.1.219

    PubMed  CAS  Article  Google Scholar 

  7. 7.

    P. M. Mendelman A. L. Smith J. Levy A. Weber B. Ramsey R. L. Davis (1985) ArticleTitleAminoglycoside penetration, inactivation, an efficacy in cystic fibrosis sputum Am. Rev. Respir. Dis. 132 761–765 Occurrence Handle3931522 Occurrence Handle1:CAS:528:DyaL2MXmtVGks78%3D

    PubMed  CAS  Google Scholar 

  8. 8.

    L. Saiman (1998) ArticleTitleUse of aerolized antibiotics in patients with cystic fibrosis Pediatr. Infect. Dis. J. 17 158–159 Occurrence Handle9493815 Occurrence Handle1:STN:280:DyaK1c7lt1yjuw%3D%3D Occurrence Handle10.1097/00006454-199802000-00016

    PubMed  CAS  Article  Google Scholar 

  9. 9.

    C. H. Feng S. J. Lin H. L. Wu S. H. Chen (2002) ArticleTitleTrace analysis of tobramycin in human plasma by derivatization and high-performance liquid chromatography with ultraviolet detection J. Chromatogr. B. 780 349–354 Occurrence Handle1:CAS:528:DC%2BD38Xptlans7o%3D Occurrence Handle10.1016/S1570-0232(02)00544-5

    CAS  Article  Google Scholar 

  10. 10.

    J. Sham Y. Zhang W. Finlay W. Roa R. Löbenberg (2004) ArticleTitleFormulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung Int. J. Pharm. 269 457–467 Occurrence Handle14706257 Occurrence Handle1:CAS:528:DC%2BD3sXhtVWjsrzJ Occurrence Handle10.1016/j.ijpharm.2003.09.041

    PubMed  CAS  Article  Google Scholar 

  11. 11.

    M. Newhouse P. Hirst S. Duddu Y. Walter T. Tarara A. Clark J. Weers (2003) ArticleTitleInhalation of a dry powder tobramycin pulmosphere formulation in healthy volunteers Chest 124 360–366 Occurrence Handle12853545 Occurrence Handle1:CAS:528:DC%2BD3sXmsFClt7s%3D Occurrence Handle10.1378/chest.124.1.360

    PubMed  CAS  Article  Google Scholar 

  12. 12.

    H. Steckel H. Brandes (2004) ArticleTitleA novel spray-drying technique to produce low density particles for pulmonary delivery Int. J. Pharm. 278 187–195 Occurrence Handle15158961 Occurrence Handle1:CAS:528:DC%2BD2cXktFOiu7o%3D Occurrence Handle10.1016/j.ijpharm.2004.03.010

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    M. Irngartinger V. Camuglia M. Damn J. Goede H. W. Frijlink (2004) ArticleTitlePulmonary delivery of therapeutic peptides via dry powder inhalation: effects of micronisation and manufacturing Eur. J. Pharm. Biopharm. 58 7–14 Occurrence Handle15207532 Occurrence Handle1:CAS:528:DC%2BD2cXltVGht7Y%3D Occurrence Handle10.1016/j.ejpb.2004.03.016

    PubMed  CAS  Article  Google Scholar 

  14. 14.

    R. J. Malcomson J. K. Embleton (1998) ArticleTitleDry powder formulations for pulmonary delivery Pharm. Sci. Tech. Today 1 394–398 Occurrence Handle10.1016/S1461-5347(98)00099-6

    Article  Google Scholar 

  15. 15.

    J. G. Weers (2000) ArticleTitleDispersible powders for inhalation applications Innov. Pharm. Technol. 1 111–116 Occurrence Handle1:CAS:528:DC%2BD3MXktlemt70%3D

    CAS  Google Scholar 

  16. 16.

    J. C. Feeley P. York B. S. Sumby H. Dicks (1998) ArticleTitleDetermination of surface properties and flow characteristics of salbutamol sulphate, before and after micronisation Int. J. Pharm. 172 89–96 Occurrence Handle1:CAS:528:DyaK1cXls1equrc%3D Occurrence Handle10.1016/S0378-5173(98)00179-3

    CAS  Article  Google Scholar 

  17. 17.

    A. Chawla K. M. G. Taylor J. M. Newton M. C. R. Johnson (1994) ArticleTitleProduction of spray-dried salbutamol sulphate for use in dry powder aerosol formulations Int. J. Pharm. 108 233–240 Occurrence Handle1:CAS:528:DyaK2cXkvFWlsb8%3D Occurrence Handle10.1016/0378-5173(94)90132-5

    CAS  Article  Google Scholar 

  18. 18.

    L. A. Dellamary T. E. Tarara C. H. Woelk A. Adractas M. L. Costello H. Gill J. G. Weers (2000) ArticleTitleHollow porous particles in metered dose inhalers Pharm. Res. 17 168–174 Occurrence Handle10751031 Occurrence Handle1:CAS:528:DC%2BD3cXitVOqur4%3D Occurrence Handle10.1023/A:1007513213292

    PubMed  CAS  Article  Google Scholar 

  19. 19.

    A. J. Hickey T. B. Martonen Y. Yang (1996) ArticleTitleTheoretical relationship of lung deposition to the fine particle fraction of inhalation aerosols Pharm. Acta Helv. 71 185–190 Occurrence Handle8818308 Occurrence Handle1:CAS:528:DyaK28XlvFOmsLo%3D Occurrence Handle10.1016/0031-6865(96)00014-3

    PubMed  CAS  Article  Google Scholar 

  20. 20.

    J. Elversson A. Millqvist-Fureby G. Alderborn U. Elofsson (2003) ArticleTitleDroplet and particle size relationship and shell thickness of inhalable lactose particles during spray-drying J. Pharm. Sci. 92 900–910 Occurrence Handle12661075 Occurrence Handle1:CAS:528:DC%2BD3sXislOgsLs%3D Occurrence Handle10.1002/jps.10352

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    C. Bosquillon P. Rouxhet F. Ahimou D. Simon C. Culot V. Préat R. Vanbever (2004) ArticleTitleAerosolization properties, surface composition and physical state of spray-dried protein powders J.Control. Release 99 357–367 Occurrence Handle15451594 Occurrence Handle1:CAS:528:DC%2BD2cXnvVCjs78%3D Occurrence Handle10.1016/j.jconrel.2004.07.022

    PubMed  CAS  Article  Google Scholar 

  22. 22.

    J. Heyder J. Gebhart G. Rudolf C. F. Schiller W. Stahlhofen (1986) ArticleTitleDeposition of particles in the human respiratory tract in the size range 0.005–15 μm J. Aerosol Sci. 17 811–825 Occurrence Handle10.1016/0021-8502(86)90035-2

    Article  Google Scholar 

  23. 23.

    Th. Sebti K. Amighi (1993) ArticleTitleSolid lipid particles as pharmaceutically acceptable fillers or carriers for inhalation, abstract in Pharmaceutical Sciences Fair & Exhibition, June 12–17 2005 Nice, France Exp. Lung Res. 19 1–19

    Google Scholar 

  24. 24.

    M. A. Myers D. A. Thomas L. Straub W. Soucy R. W. Niven M. Kaltenbach C. I. Hood H. Schreir R. J. Gonzalez-Rothi (1993) ArticleTitlePulmonary effects of chronic exposure to liposome aerosols in mice Exp. Lung Res. 19 1–19 Occurrence Handle8440200 Occurrence Handle1:STN:280:ByyC2sfjslI%3D

    PubMed  CAS  Google Scholar 

  25. 25.

    T. R. Desai J. P. Wong R. E. W. Hancock W. H. Finlay (2001) ArticleTitleA novel approach to the pulmonary delivery of liposomes in dry powder form to eliminate the deleterious effects of milling J. Pharm. Sci. 91 IssueID2 482–491 Occurrence Handle10.1002/jps.10021

    Article  Google Scholar 

  26. 26.

    A. Haynes M. S. Shaik H. Krapup M. Singh (2004) ArticleTitleEvaluation of the Malvern Spraytec® with inhalation cell for the measurement of particle size distribution from metered dose inhalers J. Pharm. Sci. 93 IssueID2 349–363 Occurrence Handle14705192 Occurrence Handle1:CAS:528:DC%2BD2cXhsFagu7Y%3D Occurrence Handle10.1002/jps.10558

    PubMed  CAS  Article  Google Scholar 

  27. 27.

    T. A. Standaert D. Vandevanter B. W. Ramsey M. Vasiljev P. Nardella D. Gmur C. Bredl A. Murphy A. B. Montgomery (2000) ArticleTitleThe choice of compressor effects the aerosol parameters and the delivery of tobramycin from a single model nebulizer J. Aerosol Med. 13 IssueID2 147–153 Occurrence Handle11010595 Occurrence Handle1:STN:280:DC%2BD3M%2Fgs1eksw%3D%3D Occurrence Handle10.1089/089426800418677

    PubMed  CAS  Article  Google Scholar 

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Correspondence to Karim Amighi.

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Pilcer, G., Sebti, T. & Amighi, K. Formulation and Characterization of Lipid-Coated Tobramycin Particles for Dry Powder Inhalation. Pharm Res 23, 931–940 (2006).

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Key Words

  • dry powder inhaler (DPI)
  • lipid-coated particles
  • pulmonary delivery
  • spray drying
  • tobramycin