title: On-line monitoring of blend uniformity in continuous drug product manufacturing process--The impact of powder flow rate and the choice of spectrometer: Dispersive vs. FT.
abstract: One of the commonly acknowledged issues in continuous manufacturing of drug products is how to provide a representative sampling on flowing powder to assure its blend uniformity. An investigation was conducted to improve understanding on the impact of powder flow rate under different continuous manufacturing conditions and the impact of optical parameters (such as resolution, co-adds, and integration time) on NIR spectral quality with respect to a dispersive and a Fourier transform instrument. A partial least squares (PLS)-based spectral pretreatment was found useful to tackle the impact of different flow rates on NIR spectral signals. Multivariate figures of merit (FOM) were used to evaluate performances across different instruments and optical settings and discover the advantageous selectivity and sensitivity on the Fourier transform than the dispersive instrument regardless of the use of co-adds.
authors.affiliation: Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285, USA. Electronic address: shi_zhenqi@lilly.com.
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: McGhehey
authors.affiliation: Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Leavesley
authors.affiliation: Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Leo F
authors.initials: LF
authors.lastname: Manley
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D017022:Flow Injection Analysis / Q000379:methods / Q000592:standards; D016018:Least-Squares Analysis; D011208:Powders / Q000032:analysis* / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods* / Q000592:standards
chemical_list: D011208:Powders
keywords: Blending uniformity; Continuous manufacturing process; Multivariate figures of merit; Near infrared spectroscopy; Process analytical technology