title: Simple and scalable method for peptide inhalable powder production.
abstract: The aim of this work was to produce capreomycin dry powder and capreomycin loaded PLGA microparticles intended for tuberculosis inhalation therapy, using simple and scalable methods. Capreomycin physico-chemical characteristics have been modified by hydrophobic ion pairing with oleate. The powder suspension was processed by high pressure homogenization and spray-dried. Spray-drying was also used to prepare capreomycin oleate (CO) loaded PLGA microparticles. CO powder was suspended in the organic phase containing PLGA and the suspension was spray-dried. Particle dimensions were determined using photon correlation spectroscopy and Accusizer C770. Morphology was investigated by scanning electron microscopy (SEM) and capreomycin content by spectrophotometry. Capreomycin properties were modified to increase polymeric microparticle content and obtain respirable CO powder. High pressure homogenization allowed to reduce CO particle dimensions obtaining a population in the micrometric (6.18 microm) and one in the nanometric (approximately 317 nm) range. SEM pictures showed not perfectly spherical particles with a wrinkled surface, generally suitable for inhalation. PLGA particles were characterized by a high encapsulation efficiency (about 90%) and dimensions (approximately 6.69 microm) suitable for inhalation. Concluding, two different formulations were successfully developed for capreomycin pulmonary delivery. The hydrophobic ion pair strategy led to a noticeable drug content increase.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Via del Liceo 1, 06123 Perugia, Italy. lululi@unipg.it
authors.forename: Aurélie
authors.initials: A
authors.lastname: Schoubben
authors.forename: Paolo
authors.initials: P
authors.lastname: Blasi
authors.forename: Stefano
authors.initials: S
authors.lastname: Giovagnoli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ricci
authors.forename: Carlo
authors.initials: C
authors.lastname: Rossi
mesh_terms: D000280:Administration, Inhalation; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002207:Capreomycin / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D019301:Oleic Acid / Q000737:chemistry; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011208:Powders / Q000138:chemical synthesis*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
chemical_list: D000904:Antibiotics, Antitubercular; D001672:Biocompatible Materials; D010455:Peptides; D011208:Powders; D002207:Capreomycin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019301:Oleic Acid; D019344:Lactic Acid; C013173:osteum