title: Comparison of high-resolution ultrasonic resonator technology and Raman spectroscopy as novel process analytical tools for drug quantification in self-emulsifying drug delivery systems.
abstract: Self-emulsifying drug delivery systems (SEDDS) are complex mixtures in which drug quantification can become a challenging task. Thus, a general need exists for novel analytical methods and a particular interest lies in techniques with the potential for process monitoring. This article compares Raman spectroscopy with high-resolution ultrasonic resonator technology (URT) for drug quantification in SEDDS. The model drugs fenofibrate, indomethacin, and probucol were quantitatively assayed in different self-emulsifying formulations. We measured ultrasound velocity and attenuation in the bulk formulation containing drug at different concentrations. The formulations were also studied by Raman spectroscopy. We used both, an in-line immersion probe for the bulk formulation and a multi-fiber sensor for measuring through hard-gelatin capsules that were filled with SEDDS. Each method was assessed by calculating the relative standard error of prediction (RSEP) as well as the limit of quantification (LOQ) and the mean recovery. Raman spectroscopy led to excellent calibration models for the bulk formulation as well as the capsules. The RSEP depended on the SEDDS type with values of 1.5-3.8%, while LOQ was between 0.04 and 0.35% (w/w) for drug quantification in the bulk. Similarly, the analysis of the capsules led to RSEP of 1.9-6.5% and LOQ of 0.01-0.41% (w/w). On the other hand, ultrasound attenuation resulted in RSEP of 2.3-4.4% and LOQ of 0.1-0.6% (w/w). Moreover, ultrasound velocity provided an interesting analytical response in cases where the drug strongly affected the density or compressibility of the SEDDS. We conclude that ultrasonic resonator technology and Raman spectroscopy constitute suitable methods for drug quantification in SEDDS, which is promising for their use as process analytical technologies.
authors.affiliation: Institute of Pharmaceutical Technology, University of Applied Sciences Northwestern Switzerland, Gründenstrasse 40, 4132 Muttenz, Switzerland.
authors.forename: Cordula
authors.initials: C
authors.lastname: Stillhart
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D002138:Calibration; D002214:Capsules; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D011345:Fenofibrate / Q000008:administration & dosage / Q000032:analysis; D007213:Indomethacin / Q000008:administration & dosage / Q000032:analysis; D057230:Limit of Detection; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000032:analysis*; D011341:Probucol / Q000008:administration & dosage / Q000032:analysis; D012015:Reference Standards; D012995:Solubility; D013016:Sound; D013059:Spectrum Analysis, Raman / Q000295:instrumentation / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D002214:Capsules; D004655:Emulsions; D004364:Pharmaceutical Preparations; D011341:Probucol; D011345:Fenofibrate; D007213:Indomethacin