Condensational growth of combination drug-excipient submicrometer particles for targeted high-efficiency pulmonary delivery: evaluation of formulation and delivery device

J Pharm Pharmacol. 2012 Sep;64(9):1254-63. doi: 10.1111/j.2042-7158.2012.01476.x. Epub 2012 Feb 21.

Abstract

Objectives: The objective of this study was to investigate the in-vitro particle-size growth of combination drug and excipient submicrometer aerosols generated from a series of formulations and two aerosol delivery devices.

Methods: Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Budesonide and albuterol sulfate were used as model drugs and were formulated with sodium chloride, citric acid and mannitol as excipients in various ratios. Aerosol growth was evaluated in-vitro in a coiled-tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways.

Key findings: Submicrometer combination drug : excipient aerosols when exposed to simulated respiratory conditions increased to micrometer size suitable for pulmonary deposition. It was possible to control the aerosol growth ratio by altering: (1) the hygroscopic excipient, (2) the drug : excipient ratio and (3) the drug. The applicability of this approach was demonstrated using the capillary aerosol generator and the Respimat inhaler.

Conclusions: The enhanced excipient growth approach may enable the delivery of submicrometer aerosol particles that increase in size within the airways and result in high percentages of pulmonary deposition.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Albuterol / administration & dosage
  • Albuterol / chemistry
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / chemistry
  • Budesonide / administration & dosage
  • Budesonide / chemistry
  • Chemistry, Pharmaceutical
  • Citric Acid / chemistry
  • Drug Combinations
  • Drug Delivery Systems*
  • Excipients / chemistry*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Lung / metabolism*
  • Mannitol / chemistry
  • Metered Dose Inhalers*
  • Models, Anatomic
  • Nanoparticles / chemistry*
  • Particle Size
  • Respiratory Mucosa / metabolism*
  • Sodium Chloride / chemistry

Substances

  • Aerosols
  • Bronchodilator Agents
  • Drug Combinations
  • Excipients
  • Citric Acid
  • Mannitol
  • Sodium Chloride
  • Budesonide
  • Albuterol