title: Poly(ethylene carbonate) microspheres: manufacturing process and internal structure characterization.
abstract: The granulocyte-macrophage colony stimulating factor (GM-CSF), a water-soluble cytokine, was encapsulated in poly(ethylene carbonate) microspheres (MS) by a double emulsion w(1)/o/w(2) solvent evaporation method. Poly(ethylene carbonate) is a new polymer of high molecular weight (MW) and forms polymer matrices that are exclusively surface bioerodible. In the frame of this study, the influence of the polymer molecular weight and the polymer concentration in the organic phase on the physico-chemical characteristics of the microspheres were investigated. Ninety percent of the microspheres had a diameter ranging between 4 and 136 microm, with a mean value of 30 microm. The encapsulation ratios ranged from 2.22 to 2.51% (w/w) depending on the molecular weight of the polymer corresponding to an encapsulation efficiency of 70 to 100%, respectively. Independent of the polymer molecular weight used, the in vitro drug release was very low, ranging from 5.61 to less than 1% of the total encapsulated GM-CSF amount. Scanning electron microscopy (SEM) analysis showed microparticles with spherical shapes and smooth surfaces containing a few small globules. The inner structure of the microspheres appeared to consist of a polymeric matrix surrounding numerous globules. These globules have different sizes, shape and distribution in the polymeric matrix, depending on the concentration of the polymer solution and on the polymer molecular weight. In addition, it was demonstrated that the GM-CSF lowered the interfacial tension between the GM-CSF aqueous solution and the methylene chloride organic phase. The active critical concentration was as low as 0.008 mg/ml. It was therefore suggested that this particular behavior contributed to the stabilization of the primary emulsion during the formation of the microspheres, leading to rather high encapsulation efficiency.
authors.affiliation: Novartis Pharma AG, Pharmaceutical Development, CH-4002, Basel, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Lambert
authors.forename: O
authors.initials: O
authors.lastname: Nagele
authors.forename: V
authors.initials: V
authors.lastname: Loux
authors.forename: J D
authors.initials: JD
authors.lastname: Bonny
authors.forename: L
authors.initials: L
authors.lastname: Marchal-Heussler
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004339:Drug Compounding; D004355:Drug Stability; D004655:Emulsions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000097:blood; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011095:Polyethylenes / Q000737:chemistry*; D012996:Solutions; D013500:Surface Tension; D014783:Viscosity
chemical_list: D004655:Emulsions; D011095:Polyethylenes; D012996:Solutions; C039212:polyethylene carbonate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor