Raman spectroscopy for in-line and off-line quantification of poorly soluble drugs in strip films

Jun Zhang, Ye Ying, Barbara Pielecha-Safira, Ecevit Bilgili, Rohit Ramachandran, Rodolfo Romañach, Rajesh N. Davé, Zafar Iqbal

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 (R2) 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.

Original languageEnglish (US)
Pages (from-to)428-437
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume475
Issue number1
DOIs
StatePublished - Nov 20 2014

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Calibration model
  • In-line drug concentration monitoring
  • Principal component analysis
  • Raman spectroscopy
  • Strip films

Fingerprint

Dive into the research topics of 'Raman spectroscopy for in-line and off-line quantification of poorly soluble drugs in strip films'. Together they form a unique fingerprint.

Cite this