title: Raman spectroscopy for in-line and off-line quantification of poorly soluble drugs in strip films.
abstract: Raman spectroscopy was used as a process analytical technology (PAT) tool for in-line measurement of active pharmaceutical ingredient (API) content during continuous manufacturing of strip films containing nanoparticles of poorly water-soluble APIs. Fenofibrate and naproxen were used as model APIs, whose concentrations ranged from 3% to 26% (w/w) in the model calibration. For both in-line and off-line measurements, calibration models employed partial least square (PLS) analysis, yielding correlation coefficients (R(2)) greater than 0.9946 and root mean squared error of calibration (RMSEC) of about 0.44%, indicating the validity and accuracy of the calibration. The robustness of Raman spectroscopy as a PAT tool was established by considering three processing parameters after substrate interference correction: sensing location, substrate speed and film thickness. Calibration models for each API were validated using a separate batch of strip films by predicting the API concentrations to within ±1.3%. Principal component analysis (PCA) was used to explain the interactions between processing variables and calibration models, which suggest that besides API concentration, film thickness could also be monitored using Raman spectroscopy. The results demonstrate the potential of Raman spectroscopy as an effective PAT tool for novel strip film manufacturing process, facilitating detection of drug form and concentration in real-time.
authors.affiliation: Department of Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Ying
authors.affiliation: Wallington Public School, Pine Street, Wallington, NJ 07057, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pielecha-Safira
authors.affiliation: Department of Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Ecevit
authors.initials: E
authors.lastname: Bilgili
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Department of Chemistry, University of Puerto Rico, Mayagüez Campus, Puerto Rico, USA.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Romañach
authors.affiliation: Department of Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA. Electronic address: Dave@njit.edu.
authors.forename: Rajesh N
authors.initials: RN
authors.lastname: Davé
authors.affiliation: Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ 07102, USA. Electronic address: zafar.iqbal@njit.edu.
authors.forename: Zafar
authors.initials: Z
authors.lastname: Iqbal
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical; D011345:Fenofibrate / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry; D025341:Principal Component Analysis; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D009288:Naproxen; D011345:Fenofibrate
keywords: Calibration model; In-line drug concentration monitoring; Principal component analysis; Raman spectroscopy; Strip films