title: Confocal Raman microscopy to probe content uniformity of a lipid based powder for inhalation: a quality by design approach.
abstract: In the present work confocal Raman microscopy was employed as a non-destructive tool to define the content uniformity and the polymorphic form of a drug substance distributed within a lipid based inhalable powder. Two spray dried powders with different active ingredient concentrations (1.55 and 7.3wt/wt%) and an additional placebo formulation were analyzed with confocal Raman microscopy and scanning electron microscopy to define the distribution of active substance within the lipid based particles as well as its polymorphic form. The formulation containing less drug substance was shown to have a high degree of content uniformity: a complete colocalization of the Raman signal for the lipids and the Raman signal for the drug substance was detected, implying that the active ingredient was homogenously distributed within the lipid particles. Within the higher concentrated preparation, in addition to the colocalized active ingredient, Raman signals of crystalline drug substance could be observed which were not matching with the location of the consistent lipid signal. Those observations gave evidence that a part of the active substance in this formulation was not molecularly dispersed within the powder. It could be shown that confocal Raman microscopy may be used as a fast and convenient method to define the content uniformity of an active ingredient within a lipid based spray dried powder for inhalation. Using this technique the distribution of an active ingredient can be characterized non-destructively, aiding in the understanding of complex drug delivery systems e.g. in the field of inhalable pharmaceutical powders. In addition analysis of solid state is available with confocal Raman microscopy.
authors.affiliation: Novartis Pharma AG, Technical Research & Development, Basel, Switzerland.
authors.forename: Carina
authors.initials: C
authors.lastname: Schoenherr
authors.forename: Thomas
authors.initials: T
authors.lastname: Haefele
authors.forename: Kurt
authors.initials: K
authors.lastname: Paulus
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Francese
mesh_terms: D000280:Administration, Inhalation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002784:Cholesterol / Q000737:chemistry; D008027:Light; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry*; D018613:Microscopy, Confocal / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry; D011786:Quality Control; D012542:Scattering, Radiation; D013059:Spectrum Analysis, Raman; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D008055:Lipids; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011208:Powders; D053835:Unilamellar Liposomes; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D002784:Cholesterol