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Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized Bed Design

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Abstract

The objective of this study was to develop a new high-efficiency dry powder inhaler (DPI) that can effectively aerosolize large masses (25–100 mg) of spray dried powder formulations. The DPI was designed to implement a concept similar to a fluidized bed for aerosolization using small mixing balls made of polytetrafluoroethylene along with a larger, hollow dosing sphere filled with the powder. The performance of the fluidized bed DPI was compared, based on emitted dose (ED) and aerosolization efficiency, to other recently developed capsule-based DPIs that were designed to accommodate smaller powder masses (~2–20 mg). The inhalers were tested with spray dried excipient enhanced growth (EEG) formulations that contained an antibiotic (ciprofloxacin) and hygroscopic excipient (mannitol). The new fluidized bed design produced an ED of 71% along with a mass median aerodynamic diameter of 1.53 μm and fine particle fractions <5 and 1 μm of 93 and 36%, respectively, when used to deliver a 100 mg loaded mass of EEG powder with the advantage of not requiring multiple capsules. Surprisingly, performance of the device was further improved by removing the mixing balls from the inhaler and only retaining the dose containment sphere.

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Abbreviations

AS:

Albuterol sulfate

Cipro:

Ciprofloxacin hydrochloride

DPI:

Dry powder inhaler

ED:

Emitted dose

EEG:

Excipient enhanced growth

FB:

Fluidized bed

FPF:

Fine particle fraction

HPLC:

High-performance liquid chromatography

HPMC:

Hydroxypropyl methylcellulose

MMAD:

Mass median aerodynamic diameter

MT:

Mouth-throat

PTFE:

Polytetraflouroethylene

PVDF:

Polyvinylidene fluoride

SD:

Standard deviation

References

  1. Behara, S. R. B., D. R. Farkas, M. Hindle, and P. W. Longest. Development of a high efficiency dry powder inhaler: effects of capsule chamber design and inhaler surface modifications. Pharm. Res. 31:360–372, 2014.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Behara, S. R. B., P. W. Longest, D. R. Farkas, and M. Hindle. Development and comparison of new high-efficiency dry powder inhalers for carrier-free formulations. J. Pharm. Sci. 103:465–477, 2014.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Below, A., D. Bickmann, and J. Breitkreutz. Assessing the performance of two dry powder inhalers in preschool children using an idealized pediatric upper airway model. Int. J. Pharm. 444(1–2):169–174, 2013.

    Article  CAS  PubMed  Google Scholar 

  4. Bilton, D., P. Robinson, P. Cooper, C. G. Gallagher, J. Kolbe, H. Fox, A. Jaques, and B. Charlton. Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study. Eur. Respir. J. 38(5):1071–1080, 2011.

    Article  CAS  PubMed  Google Scholar 

  5. Corcoran, T. E., R. Venkataramanan, R. M. Hoffman, M. P. George, A. Petrov, T. Richards, S. Zhang, J. Choi, Y. Y. Gao, C. D. Oakum, R. O. Cook, and M. Donahoe. Systemic delivery of atropine sulfate by the microdose dry-powder inhaler. J. Aerosol. Med. Pulm. Drug Deliv. 26(1):46–55, 2013.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. de Boer, A. H., P. Hagedoorn, R. Woolhouse, and E. Wynn. Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer™ disposable high-dose dry powder inhaler. J. Pharm. Pharmacol. 64(9):1316–1325, 2012.

    Article  PubMed  Google Scholar 

  7. Geller, D. E., J. Weers, and S. Heuerding. Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere™ technology. J. Aerosol. Med. Pulm. Drug Deliv. 24(4):175–182, 2011.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Grasmeijer, F., P. Hagedoorn, H. W. Frijlink, and A. H. de Boer. Characterisation of high dose aerosols from dry powder inhalers. Int. J. Pharm. 437(1–2):242–249, 2012.

    Article  CAS  PubMed  Google Scholar 

  9. Green, D. W. Perry’s Chemical Engineers’ Handbook (7th ed.). New York: McGraw-Hill, 1997.

    Google Scholar 

  10. Hindle, M., and P. W. Longest. Condensational growth of combination drug-excipient submicrometer particles for targeted high efficiency pulmonary delivery: evaluation of formulation and delivery device. J. Pharm. Pharmacol. 64(9):1254–1263, 2012.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Hindle, M., and P. W. Longest. Quantitative analysis and design of a spray aerosol inhaler. Part 2: improvements in mouthpiece performance. J. Aerosol. Med. Pulm. Drug Deliv. 26(5):237–247, 2013.

    Article  CAS  PubMed  Google Scholar 

  12. Hinds, W. C. Aerosol Technology: Properties, Behavior, and Measurement of Airborne Particles. New York: Wiley, 1999.

    Google Scholar 

  13. ICRP. Human Respiratory Tract Model for Radiological Protection. New York: Elsevier Science Ltd., 1994.

    Google Scholar 

  14. Islam, N., and M. J. Cleary. Developing an efficient and reliable dry powder inhaler for pulmonary drug delivery—a review for multidisciplinary researchers. Med. Eng. Phys. 34:409–427, 2012.

    Article  PubMed  Google Scholar 

  15. Keller, Manfred., and Joerg. Schierholz. Have inadequate delivery systems hampered the clinical success of inhaled disodium cromoglycate? Time for reconsideration. Expert Opin. Drug Deliv. 8(1):1–17, 2010.

    Article  Google Scholar 

  16. Lind, T., S. Danner, and S. Guentay. Monodisoerse fine aerosol generation using fluidized bed. Powder Technol. 199(3):232–237, 2010.

    Article  CAS  Google Scholar 

  17. Longest, P. W., and M. Hindle. Quantitative analysis and design of a spray aerosol inhaler. Part 1: effects of dilution air inlets and flow paths. J. Aerosol. Med. Pulm. Drug Deliv. 22(3):271–283, 2009.

    Article  PubMed  Google Scholar 

  18. Longest, P. W., Y.-J. Son, L. T. Holbrook, and M. Hindle. Aerodynamic factors responsible for the deaggregation of carrier-free drug powders to form micrometer and submicrometer aerosols. Pharm. Res. 30:1608–1627, 2013.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Prenni, A. J., R. L. Siefert, T. B. Onasch, M. A. Tolbert, and P. J. DeMott. Design and characterization of a fluidized bed aerosol generator: a source for dry, submicrometer aerosol. Aerosol Sci. Technol. 32(5):465–481, 2000.

    Article  CAS  Google Scholar 

  20. Prime, D., A. C. Grant, A. L. Slater, and R. N. Woodhouse. A critical comparison of the dose delivery characteristics of four alternative inhalation devices delivering salbutamol: pressurized metered dose inhaler, Diskus inhaler, Diskhaler inhaler, and Turbuhaler inhaler. J. Aerosol Med. 12(2):75–84, 1999.

    Article  CAS  PubMed  Google Scholar 

  21. Rissler, Jenny., Lars. Asking, and Jakob. Kisbye Dreyer. A methodology to study impactor particle reentrainment and a proposed stage coating for the NGI. J. Aerosol. Med. Pulm. Drug Deliv. 22(4):309–316, 2009.

    Article  CAS  PubMed  Google Scholar 

  22. Ruppert, C., T. Kuchenbuch, M. Boensch, S. Schmidt, U. Mathes, V. Hillebrand, I. Henneke, P. Markart, I. Reiss, R. T. Schermuly, W. Seeger, and A. Gunther. Dry powder aerosolization of a recombinant surfactant protein-C-based surfactant for inhalative treatment of the acutely inflamed lung. Crit. Care Med. 38(7):1584–1591, 2010.

    Article  CAS  PubMed  Google Scholar 

  23. Sham, J. O.-H., Y. Zhang, W. H. Finlay, W. H. Roa, and R. Lobenberg. Formulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung. Int. J. Pharm. 269:457–467, 2004.

    Article  CAS  PubMed  Google Scholar 

  24. Smith, I. J., J. Bell, N. Bowman, M. Everard, S. Stein, and J. G. Weers. Inhaler devices: what remains to be done? J. Aerosol. Med. Pulm. Drug Deliv. 23:S25–S37, 2010.

    Article  PubMed  Google Scholar 

  25. Son, Y.-J., P. W. Longest, and M. Hindle. Aerosolization characteristics of dry powder inhaler formulations for the excipient enhanced growth (EEG) application: effect of spray drying process conditions on aerosol performance. Int. J. Pharm. 443:137–145, 2013.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Son, Y.-J., P. W. Longest, G. Tian, and M. Hindle. Evaluation and modification of commercial dry powder inhalers for the aerosolization of submicrometer excipient enhanced growth (EEG) formulation. Eur. J. Pharm. Sci. 49:390–399, 2013.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Tian, G., P. W. Longest, X. Li, and M. Hindle. Targeting aerosol deposition to and within the lung airways using excipient enhanced growth. J. Aerosol. Med. Pulm. Drug Deliv. 26(5):248–265, 2013.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Tiddens, H. A., D. E. Geller, P. Challoner, R. J. Speirs, K. C. Kesser, S. E. Overbeek, D. Humble, S. B. Shrewsbury, and T. A. Standaert. Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes of cystic fibrosis patients of six years and older. J. Aerosol Med. Depos. Clear. Eff. Lung 19(4):456–465, 2006.

    Article  CAS  Google Scholar 

  29. Weers, J. G., R. C. Andrew, N. Rao, K. Ung, A. Haynes, S. K. Khindri, S. A. Perry, S. Machineni, and P. Colthorpe. In vitro–in vivo correlations observed with indacaterol-based formulations delivered with the breezhaler®. J. Aerosol. Med. Pulm. Drug Deliv. 2014.

  30. Young, P. M., J. Crapper, G. Philips, K. Sharma, H.-K. Chan, and D. Traini. Overcoming dose limitaitons using the orbital multi-breath dry powder inhaler. J. Aerosol. Med. Pulm. Drug Deliv. 26:1–10, 2013.

    Article  Google Scholar 

  31. Zhou, Qi., Patricia. Tang, Sharon. Shui. Yee. Leung, John. Gar. Yan. Chan, and Hak.-Kim. Chan. Emerging inhalation aerosol devices and strategies: where are we headed? Adv. Drug Deliv. Rev. 75:3–17, 2014.

    Article  CAS  PubMed  Google Scholar 

  32. Zhu, J., and Y. Ma. A New breath-activated, excipient-free dry powder inhaler and a rotating fluidized bed powder dispenser for pulmonary drug delivery. Respir. Drug Deliv. 925–930:2006, 2006.

    Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge financial support from the National Heart, Lung, and Blood Institute through Award R01 HL107333. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health.

Conflict of interest

The authors are employees of Virginia Commonwealth University. Virginia Commonwealth University is seeking patent protection with respect to the technology described, which if licensed may result in a financial interest to the authors.

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Authors and Affiliations

  1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, VA, 23284-3015, USA

    Dale R. Farkas & P. Worth Longest

  2. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA

    Michael Hindle & P. Worth Longest

Authors
  1. Dale R. Farkas
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  2. Michael Hindle
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  3. P. Worth Longest
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Correspondence to P. Worth Longest.

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Associate Editor John H. Linehan oversaw the review of this article.

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Farkas, D.R., Hindle, M. & Longest, P.W. Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized Bed Design. Ann Biomed Eng 43, 2804–2815 (2015). https://doi.org/10.1007/s10439-015-1335-2

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  • DOI: https://doi.org/10.1007/s10439-015-1335-2

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