Evaluation of in-line raman spectroscopic monitoring of size reduction during wet media milling of biopharmaceutics classification system class II drugs

Ye Ying, Afolawemi Afolabi, Ecevit Bilgili, Zafar Iqbal

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The aim of this study was to evaluate in-line Raman spectroscopy for monitoring the progress of particle size reduction in real time during wet-stirred media milling of two Biopharmaceutics Classification System (BCS) Class II drugs, griseofulvin and naproxen. To develop a validated online Raman method, Raman analyses were carried out offline by taking samples from the mill at various milling times. A multivariate linear model (partial least squares, PLS) was fitted to the raw data obtained from the Raman measurements and good linearity between online and offline Raman spectra was found. Line intensities (I) of the in-line spectra obtained during the wet media milling were processed by multivariate analyses and correlated with both the median size (d50) and the 90% passing particle size (d90), which were measured offline by laser diffraction. A two-parameter exponential growth model of the form d = exp[A(I - I0)] was found to establish a good correlation (R2 > 0.90) as a statistically significant model with statistically significant parameters (P < 10-4). The correlations were applicable to milled suspensions with particles in the approximate size range of 0.1-6 lm for griseofulvin and 0.1-8 μm for naproxen. These results suggest that in-line Raman spectroscopy can be used to successfully monitor the progress of particle size reduction during wet media milling.

Original languageEnglish (US)
Pages (from-to)1411-1417
Number of pages7
JournalApplied Spectroscopy
Volume68
Issue number12
DOIs
StatePublished - Dec 1 2014

All Science Journal Classification (ASJC) codes

  • Instrumentation
  • Spectroscopy

Keywords

  • BCS class II drugs
  • Bioavailability enhancement
  • Biopharmaceutics classification system
  • In-line raman spectroscopy
  • Laser diffraction
  • PLS analysis
  • Partial least square analysis
  • Wet stirred media milling

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