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Formulation of insulin-loaded N-trimethyl chitosan microparticles with improved efficacy for inhalation by supercritical fluid assisted atomization.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2016 May 30; Vol. 505 (1-2), pp. 223-33. Date of Electronic Publication: 2016 Mar 29. - Publication Year :
- 2016
-
Abstract
- Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was proposed as a green technique to fabricate insulin-loaded dry powders for inhalation administration. N-trimethyl chitosan (TMC), a polymeric mucoadhesive absorption enhancer, was synthesized and successfully micronized from aqueous solution using SAA-HCM. The prepared well-defined spherical TMC microparticles with preserved structure and thermal stability were potential carriers for delivery of proteins. Then, insulin-loaded TMC microparticles with high loading efficiency were coprecipitated from aqueous solutions using SAA-HCM without use of any organic solvents. The polymer/protein ratio revealed to be a factor influencing the particle morphology, and non-coalescing composite microparticles in amorphous state mainly ranging from 1μm to 5μm could be obtained in this work. Aerodynamic properties were assessed by next generation impactor (NGI) and the mass median aerodynamic diameter (MMAD) lied inside the inhalable range of 1-5μm, while fine particle fraction (FPF) reached above 60%. The structural integrity of encapsulated insulin was confirmed by HPLC, circular dichroism and fluorescence spectroscopy. In vivo study demonstrated that TMC could enhance the absorption and bioavailability of the pulmonarily administered insulin formulation for SD rats. These results suggest that TMC microparticles could be efficiently prepared as a promising vehicle for drug delivery, and SAA-HCM is a promising technique to prepare inhalable polymer/protein composite dry powders.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Inhalation
Animals
Chemistry, Pharmaceutical methods
Chromatography, High Pressure Liquid
Circular Dichroism
Hypoglycemic Agents administration & dosage
Hypoglycemic Agents chemistry
Hypoglycemic Agents pharmacokinetics
Insulin chemistry
Insulin pharmacokinetics
Male
Microspheres
Nebulizers and Vaporizers
Particle Size
Powders
Rats
Rats, Sprague-Dawley
Spectrometry, Fluorescence
Chitosan chemistry
Drug Carriers chemistry
Drug Delivery Systems
Insulin administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 505
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 27034000
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2016.03.053