Sustained delivery by leucine-modified chitosan spray-dried respirable powders.
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.
Learoyd
Tristan P
TP
School of Life and Health Sciences, Aston University, Birmingham, UK. T.Learoyd@herts.ac.uk
Burrows
Jane L
JL
French
Eddie
E
Seville
Peter C
PC
D000280:Administration, Inhalation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D007930:Leucine / Q000008:administration & dosage* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size; D011208:Powders
D011208:Powders; D048271:Chitosan; D007930:Leucine