Raman chemical imaging for ingredient-specific particle size characterization of aqueous suspension nasal spray formulations: a progress report.
OBJECTIVE
This study was conducted to evaluate the feasibility of using Raman chemical imaging (i.e., Raman imaging microspectroscopy) to establish chemical identity, particle size and particle size distribution (PSD) for a representative corticosteroid in aqueous nasal spray suspension formulations.


METHODS
The Raman imaging PSD protocol was validated using polystyrene (PS) microsphere size standards (NIST-traceable). A Raman spectral library was developed for the active and inactive compounds in the formulation. Four nasal sprays formulated with beclomethasone dipropionate (BDP) ranging in size from 1.4 to 8.3 microm were imaged by both Raman and brightfield techniques. The Raman images were then processed to calculate the PSD for each formulation.


RESULTS
Within each region examined, active pharmaceutical ingredient (API) particles are unambiguously identified and the total number of those particles, particle size and PSD of API free of excipients and PSD of API particles adhered to other excipients are reported.


CONCLUSIONS
Good statistical agreement is obtained between the reported and measured sizes of the PS microspheres. BDP particles were clearly distinguishable from those of excipients. Raman chemical imaging (RCI) is able to differentiate between and identify the chemical makeup of multiple components in complex BDP sample and placebo mixtures. The Raman chemical imaging method (coupled Raman and optical imaging) shows promise as a method for characterizing particle size and shape of corticosteroid in aqueous nasal spray suspension formulations. However, rigorous validation of RCI for PSD analysis is incomplete and requires additional research effort. Some specific areas of concern are discussed.
Doub
William H
WH
Division of Pharmaceutical Analysis, Food and Drug Administration/CDER/OPS, St. Louis, Missouri 63101, USA. william.doub@fda.hhs.gov
Adams
Wallace P
WP
Spencer
John A
JA
Buhse
Lucinda F
LF
Nelson
Matthew P
MP
Treado
Patrick J
PJ
D000336:Aerosols; D001507:Beclomethasone / Q000032:analysis / Q000737:chemistry; D005938:Glucocorticoids / Q000032:analysis / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008863:Microspheres; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D019999:Pharmaceutical Solutions / Q000737:chemistry; D016730:Program Development; D012044:Regression Analysis; D015203:Reproducibility of Results; D013059:Spectrum Analysis, Raman / Q000379:methods* / Q000592:standards; D013535:Suspensions; D013678:Technology, Pharmaceutical / Q000379:methods / Q000592:standards; D014867:Water / Q000737:chemistry
D000336:Aerosols; D005938:Glucocorticoids; D004364:Pharmaceutical Preparations; D019999:Pharmaceutical Solutions; D013535:Suspensions; D014867:Water; D001507:Beclomethasone