title: Evaluation of infrared-reflection absorption spectroscopy measurement and locally weighted partial least-squares for rapid analysis of residual drug substances in cleaning processes.
abstract: The usefulness of infrared-reflection absorption spectroscopy (IR-RAS) for the rapid measurement of residual drug substances without sampling was evaluated. In order to realize the highly accurate rapid measurement, locally weighted partial least-squares (LW-PLS) with a new weighting technique was developed. LW-PLS is an adaptive method that builds a calibration model on demand by using a database whenever prediction is required. By adding more weight to samples closer to a query, LW-PLS can achieve higher prediction accuracy than PLS. In this study, a new weighting technique is proposed to further improve the prediction accuracy of LW-PLS. The root-mean-square error of prediction (RMSEP) of the IR-RAS spectra analyzed by LW-PLS with the new weighting technique was compared with that analyzed by PLS and locally weighted regression (LWR). The RMSEP of LW-PLS with the proposed weighting technique was about 36% and 14% smaller than that of PLS and LWR, respectively, when ibuprofen was a residual drug substance. Similarly, LW-PLS with the weighting technique was about 39% and 24% better than PLS and LWR in RMSEP, respectively, when magnesium stearate was a residual excipient. The combination of IR-RAS and LW-PLS with the proposed weighting technique is a very useful rapid measurement technique of the residual drug substances.
authors.affiliation: The Japan Society of Pharmaceutical Machinery and Engineering, Chiyoda-ku, Tokyo, Japan. nakagawa.hiroshi.w5@daiichisankyo.co.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tajima
authors.forename: Manabu
authors.initials: M
authors.lastname: Kano
authors.forename: Sanghong
authors.initials: S
authors.lastname: Kim
authors.forename: Shinji
authors.initials: S
authors.lastname: Hasebe
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakagami
mesh_terms: D004350:Drug Residues; D017743:Equipment Reuse; D005079:Excipients / Q000737:chemistry; D007052:Ibuprofen / Q000032:analysis* / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000706:statistics & numerical data; D013229:Stearic Acids / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*; D013997:Time Factors
chemical_list: D005079:Excipients; D012996:Solutions; D013229:Stearic Acids; C031183:stearic acid; D007052:Ibuprofen; D000432:Methanol