Pharmaceutical Research

, Volume 16, Issue 11, pp 1735–1742

Formulation and Physical Characterization of Large Porous Particles for Inhalation

  • Rita Vanbever
  • Jeffrey D. Mintzes
  • Jue Wang
  • Jacquelyn Nice
  • Donghao Chen
  • Richard Batycky
  • Robert Langer
  • David A. Edwards
Article

DOI: 10.1023/A:1018910200420

Cite this article as:
Vanbever, R., Mintzes, J.D., Wang, J. et al. Pharm Res (1999) 16: 1735. doi:10.1023/A:1018910200420

Abstract

Purpose. Relatively large (>5 µm) and porous (mass density < 0.4 g/cm3) particles present advantages for the delivery of drugs to the lungs, e.g., excellent aerosolization properties. The aim of this study was, first, to formulate such particles with excipients that are either FDA-approved for inhalation or endogenous to the lungs; and second, to compare the aerodynamic size and performance of the particles with theoretical estimates based on bulk powder measurements.

Methods. Dry powders were made of water-soluble excipients (e.g., lactose, albumin) combined with water-insoluble material (e.g., lung surfactant), using a standard single-step spray-drying process. Aerosolization properties were assessed with a Spinhaler TM device in vitro in both an Andersen cascade impactor and an AerosizerTM..

Results. By properly choosing excipient concentration and varying the spray drying parameters, a high degree of control was achieved over the physical properties of the dry powders. Mean geometric diameters ranged between 3 and 15 µm, and tap densities between 0.04 and 0.6 g/cm3. Theoretical estimates of mass mean aerodynamic diameter (MMAD) were rationalized and calculated in terms of geometric particle diameters and bulk tap densities. Experimental values of MMAD obtained from the AerosizerTM most closely approximated the theoretical estimates, as compared to those obtained from the Andersen cascade impactor. Particles possessing high porosity and large size, with theoretical estimates of MMAD between 1−3 µm, exhibited emitted doses as high as 96% and respirable fractions ranging up to 49% or 92%, depending on measurement technique.

Conclusions. Dry powders engineered as large and light particles, and prepared with combinations of GRAS (generally recognized as safe) excipients, may be broadly applicable to inhalation therapy.

pulmonary drug delivery dry powder large porous particles excipients aerosolization properties 

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Rita Vanbever
    • 1
    • 2
  • Jeffrey D. Mintzes
    • 2
  • Jue Wang
    • 2
  • Jacquelyn Nice
    • 2
  • Donghao Chen
    • 2
  • Richard Batycky
    • 4
  • Robert Langer
    • 1
  • David A. Edwards
    • 2
  1. 1.Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridge
  2. 2.Department of Chemical EngineeringPennsylvania State UniversityUniversity Park
  3. 3.Department of Pharmaceutical Technology, School of PharmacyUniversité catholique de LouvainBrusselsBelgium
  4. 4.Advanced Inhalation Research, Inc.Cambridge

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