Pharmaceutical Research

, Volume 26, Issue 1, pp 101–117

Templated Open Flocs of Nanorods for Enhanced Pulmonary Delivery with Pressurized Metered Dose Inhalers

  • Josh D. Engstrom
  • Jasmine M. Tam
  • Maria A. Miller
  • Robert O. WilliamsIII
  • Keith P. Johnston
Research Paper

DOI: 10.1007/s11095-008-9707-z

Cite this article as:
Engstrom, J.D., Tam, J.M., Miller, M.A. et al. Pharm Res (2009) 26: 101. doi:10.1007/s11095-008-9707-z

Abstract

Purpose

A novel concept is presented for the formation of stable suspensions composed of low density flocs of high aspect ratio drug particles in hydrofluoroalkane (HFA) propellants, and for subdividing (templating) the flocs with aerosolized HFA droplets to achieve high fine particle fractions with a pressurized metered dose inhaler.

Methods

Bovine serum albumin (BSA) nanorods, produced by thin film freezing (TFF), were added to HFA to form a suspension. Particle properties were analyzed with an Anderson cascade impactor (ACI), static and dynamic light scattering and optical microscopy.

Results

The space filling flocs in HFA were stable against settling for one year. The pMDI produced high fine particle fractions (38–47%) with an emitted dose of 0.7 mg/actuation. The atomized HFA droplets break apart, that is template, the highly open flocs. Upon evaporation of HFA, capillary forces shrink the templated flocs to produce porous particles with optimal aerodynamic diameters for deep lung delivery.

Conclusions

Open flocs composed of nanorods, stable against settling, may be templated during actuation with a pMDI to produce optimal aerodynamic diameters and high fine particle fractions. This concept is applicable to a wide variety of drugs without the need for surfactants or cosolvents to stabilize the primary particles.

KEY WORDS

bovine serum albuminflocnanorodpressurized metered dose inhalersuspension stability

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Josh D. Engstrom
    • 1
  • Jasmine M. Tam
    • 1
  • Maria A. Miller
    • 1
  • Robert O. WilliamsIII
    • 2
  • Keith P. Johnston
    • 1
  1. 1.Department of Chemical EngineeringThe University of Texas at AustinAustinUSA
  2. 2.Division of Pharmaceutics, College of PharmacyThe University of Texas at AustinAustinUSA