title: Preparation and characterization of spray-dried powders intended for pulmonary delivery of insulin with regard to the selection of excipients.
abstract: The aim of this study was to produce microparticles with optimal aerodynamic diameter for deep lung delivery (i.e., 1-3μm) of a protein drug intended for systemic absorption, using a combination of generally regarded as safe (GRAS) excipients. Based on the preliminary experiments, mannitol, l-alanine, sodium alginate, chitosan and dipalmitoylphosphatidilcholine (DPPC) were chosen as excipients and human insulin as a model protein drug. Dry powders were prepared by spray-drying. Powders with varying yields (29-80%) and low tapped densities (0.22-0.38 g/cm(3)) were obtained. Scanning electron microscopy (SEM) revealed distinctive particle morphologies among formulations from isolated spherical to highly folded particles. Aerodynamic properties were assessed by next generation impactor (NGI). Mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) ranged from 2.1 to 4.6 μm and 46 to 81%, respectively. A comparative study of protein release from microparticles was conducted in vitro using an open membrane system with more than 50% cumulative release in all formulations which followed different kinetic models. Insulin's integrity was investigated by spectrofluorimetry and electrophoresis, and no tangible changes were observed in the structure of insulin. Of the formulations studied, the third, containing mannitol/sodium alginate/insulin/sodium citrate showed promising characteristics, optimal for systemic delivery of proteins via deep lung deposition.
authors.affiliation: Student Research Committee, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Salman
authors.initials: SS
authors.lastname: Razavi Rohani
authors.affiliation: Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Student Research Committee, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: tafaghodim@mums.ac.ir.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Tafaghodi
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000464:Alginates / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002951:Citrates / Q000737:chemistry; D003890:Desiccation; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry*; D061386:Insulin, Regular, Human / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D008353:Mannitol / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D010316:Particle Size; D011208:Powders; D011994:Recombinant Proteins / Q000737:chemistry; D000077559:Sodium Citrate; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry
chemical_list: D000336:Aerosols; D000464:Alginates; D002951:Citrates; D005079:Excipients; D006603:Hexuronic Acids; D007004:Hypoglycemic Agents; D061386:Insulin, Regular, Human; D011208:Powders; D011994:Recombinant Proteins; D014867:Water; D000077559:Sodium Citrate; D008353:Mannitol; D020723:Glucuronic Acid
keywords: Chitosan; Chitosan (PubChem CID: 21896651); DPPC (PubChem CID: 452110); Dry powder inhaler; Insulin; Mannitol; Mannitol (PubChem CID: 6251); Recombinant human insulin (PubChem CID: 70678557); Sodium alginate; Sodium alginate (PubChem CID: 6850754); Sodium citrate (PubChem CID: 6224); Spray-drying; l-alanine (PubChem CID: 5950)