Journal of Pharmaceutical Sciences
Volume 93, Issue 3, 2004, Pages 635-645

Measurement of Low-Dose Active Pharmaceutical Ingredient in a Pharmaceutical Blend Using Frequency-Domain Photon Migration (Article)

Pan T. , Barber D. , Coffin-Beach D. , Sun Z. , Sevick-Muraca E.M.*
  • a Department of Chemical Engineering, Texas A and M University, College Station, TX 77843-3122, United States
  • b TorPharm, Inc., 50 Steinway Boulevard, Etobicoke, Ont. M9W 6Y3, Canada
  • c TorPharm, Inc., 50 Steinway Boulevard, Etobicoke, Ont. M9W 6Y3, Canada
  • d Malvern Instruments, Inc., 10 Southville Road, Southborough, MA 01772, United States
  • e Department of Chemical Engineering, Texas A and M University, College Station, TX 77843-3122, United States, Department of Chemistry, Texas A and M University, College Station, TX 77842-3012, United States, Photon Migration Laboratory, Texas A and M University, 1011 Richardson Building, College Station, TX 77843-3573, United States

Abstract

Frequency-domain photon migration (FDPM) measurements of time-dependent light propagation are conducted to provide the powder absorbance for quantitative prediction of terazosin as the active pharmaceutical ingredient (API) in a low-dose (0.72 wt %) oral tablet formulation. Calibration of the FDPM-derived powder absorbance at discrete wavelengths of 514, 650, 687, and 785 nm was performed for API contents ranging between 0 and 1.5 wt % in mixtures showing maximum sensitivity at 650 nm. The relative standard deviation (RSD) of FDPM absorption coefficient measurement at 650 nm in a well-mixed 1.08 wt % terazosin blend was <1.6%, of which no more than 0.12% arose from FDPM instrumental error and the remainder was attributable to the complete-random-mixture model. The applicability of FDPM as an on-line sensor for powder-blending operations was further evaluated by analyzing grab samples taken directly from five locations of a 2-cu-ft Gallay blender at intervals of 5 min within the blending process. FDPM results indicate that homogeneity was largely achieved in the first 10 min, during which the RSD of API content across five sampling locations decreased from 27% to 8%, and the RSD decreased to 5% after 25 min of blending. Evolution of homogeneity within the blending process assessed through FDPM measurements was fit to the first-order model of particle blending further evidencing applicability for monitoring powder-blending processes. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association.

Author Keywords

Blend content uniformity Photon migration Absorbance monitoring

Index Keywords

statistical analysis terazosin sampling drug mixture correlation analysis process design mathematical model excipient frequency domain photon migration particle size online analysis light absorption photon tablet formulation placebo complete random mixture model drug dose reduction Article drug activity powder
Link
https://www.scopus.com/inward/record.uri?eid=2-s2.0-1542724954&doi=10.1002%2fjps.10576&partnerID=40&md5=3b665de8f79a9e33609fb146f84ef526
DOI: 10.1002/jps.10576
ISSN: 00223549
Cited by: 18
Original Language: English