Sustained delivery of salbutamol and beclometasone from spray-dried double emulsions.
The sustained delivery of multiple agents to the lung offers potential benefits to patients. This study explores the preparation of highly respirable dual-loaded spray-dried double emulsions. Spray-dried powders were produced from water-in-oil-in-water (w/o/w) double emulsions, containing salbutamol sulphate and/or beclometasone dipropionate in varying phases. The double emulsions contained the drug release modifier polylactide co-glycolide (PLGA 50 : 50) in the intermediate organic phase of the original micro-emulsion and low molecular weight chitosan (Mw<190 kDa: emulsion stabilizer) and leucine (aerosolization enhancer) in the tertiary aqueous phase. Following spray-drying resultant powders were physically characterized: with in vitro aerosolization performance and drug release investigated using a Multi-Stage Liquid Impinger and modified USP II dissolution apparatus, respectively. Powders generated were of a respirable size exhibiting emitted doses of over 95% and fine particle fractions of up to 60% of the total loaded dose. Sustained drug release profiles were observed during dissolution for powders containing agents in the primary aqueous and secondary organic phases of the original micro-emulsion; the burst release of agents was witnessed from the tertiary aqueous phase. The novel spray-dried emulsions from this study would be expected to deposit and display sustained release character in the lung.
Learoyd
Tristan P
TP
School of Pharmacy, University of Hertfordshire, Hatfield, UK. t.learoyd@herts.ac.uk
Burrows
Jane L
JL
French
Eddie
E
Seville
Peter C
PC
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000420:Albuterol / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001507:Beclomethasone / Q000008:administration & dosage*; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004655:Emulsions / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D003692:Delayed-Action Preparations; D004655:Emulsions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D001507:Beclomethasone; D000420:Albuterol