Sustained delivery by leucine-modified chitosan spray-dried respirable powders

Int J Pharm. 2009 May 8;372(1-2):97-104. doi: 10.1016/j.ijpharm.2009.01.017. Epub 2009 Jan 24.

Abstract

The controlled co-delivery of multiple agents to the lung offers potential benefits to patients. This study investigated the preparation and characterisation of highly respirable spray-dried powders displaying the sustained release of two chemically distinct therapeutic agents. Spray-dried powders were produced from 30% (v/v) aqueous ethanol formulations that contained hydrophilic (terbutaline sulphate) and hydrophobic (beclometasone dipropionate) model drugs, chitosan (as a drug release modifier) and leucine (aerosolisation enhancer). The influence of chitosan molecular weight on spray-drying thermal efficiency, aerosol performance and drug release profile was investigated. Resultant powders were physically characterised: with in vitro aerosolisation performance and drug release profile investigated by the Multi-Stage Liquid Impinger and modified USP II dissolution apparatus, respectively. It was found that increased chitosan molecular weight gave increased spray-drying thermal efficiency. The powders generated were of a suitable size for inhalation-with emitted doses over 90% and fine particle fractions up to 72% of the loaded dose. Sustained drug release profiles were observed in dissolution tests for both agents: increased chitosan molecular weight associated with increased duration of drug release. The controlled co-delivery of hydrophilic and hydrophobic entities underlines the capability of spray drying to produce respirable particles with sustained release for delivery to the lung.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Chemistry, Pharmaceutical / methods
  • Chitosan / administration & dosage*
  • Chitosan / metabolism
  • Drug Delivery Systems / methods*
  • Leucine / administration & dosage*
  • Leucine / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Particle Size
  • Powders

Substances

  • Powders
  • Chitosan
  • Leucine