title: In situ coating--an approach for particle modification and encapsulation of proteins during spray-drying.
abstract: In this paper, we present a method for in situ coating of individual protein particles in a respirable size. The aim of the coating was to influence the particle/powder properties, and to reduce or prevent surface-induced conformational changes of the protein, during spray-drying, which was the method used for simultaneously preparing and coating particles. The investigated formulations included bovine serum albumin (BSA), trehalose and either of the two non-ionic polymers, hydroxypropyl methylcellulose (HPMC) and poly(ethylene oxide)-poly(propylene oxide) triblock co-polymer (Poloxamer 188). Complete protein coating as measured by electron spectroscopy for chemical analysis (ESCA) was achieved at a polymer concentration of approximately 1% of the total solids weight, and could be predicted from the dynamic surface tension at the air/water interface, as measured by the pendant drop method. Further, particle properties such as: size, dissolution time, powder flowability, and apparent particle density, as measured by gas pycnometry, were affected by the type and concentration of the polymer. In addition, the particle surface morphology could possibly be correlated to the surface elasticity of the droplet surface during drying. Moreover, an extensive investigation (Fourier transform infrared spectroscopy, circular dichroism and size exclusion chromatography) of the structural effects of protein encapsulated in a polymeric coating suggested that in situ coating provide particulate formulations with preserved native conformation and with a high stability during rehydration.
authors.affiliation: YKI, Institute for Surface Chemistry, PO Box 5607, SE-114 86 Stockholm, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Elversson
authors.forename: Anna
authors.initials: A
authors.lastname: Millqvist-Fureby
mesh_terms: D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D002942:Circular Dichroism; D004339:Drug Compounding / Q000379:methods*; D004548:Elasticity; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013500:Surface Tension; D014199:Trehalose / Q000737:chemistry; D014783:Viscosity
chemical_list: D004364:Pharmaceutical Preparations; D011108:Polymers; D011506:Proteins; D020442:Poloxamer; D012710:Serum Albumin, Bovine; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D014199:Trehalose