Transmission Near-Infrared (NIR) and Photon Time-of-Flight (PTOF) Spectroscopy in a Comparative Analysis of Pharmaceuticals

Abstract

We present a comprehensive study of the application of photon time-of-flight spectroscopy (PTOFS) in the wavelength range 1050-1350 nm as a spectroscopic technique for the evaluation of the chemical composition and structural properties of pharmaceutical tablets. PTOFS is compared to transmission near-infrared spectroscopy (NIRS). In contrast to transmission NIRS, PTOFS is capable of directly and independently determining the absorption and reduced scattering coefficients of the medium. Chemometric models were built on the evaluated absorption spectra for predicting tablet drug concentration. Results are compared to corresponding predictions built on transmission NIRS measurements. The predictive ability of PTOFS and transmission NIRS is comparable when models are based on uniformly distributed tablet sets. For non-uniform distribution of tablets based on particle sizes, the prediction ability of PTOFS is better than that of transmission NIRS. Analysis of reduced scattering spectra shows that PTOFS is able to characterize tablet microstructure and manufacturing process parameters. In contrast to the chemometric pseudovariables provided by transmission NIRS, PTOFS provides physically meaningful quantities such as scattering strength and slope of particle size. The ability of PTOFS to quantify the reduced scattering spectra, together with its robustness in predicting drug content, makes it suitable for such evaluations in the pharmaceutical industry.

Broadband Time Domain Diffuse Optical Reflectance Spectroscopy: A Review of Systems, Methods, and Applications

“…In this way, the uncertainties caused by variations in scattering properties could be eliminated in the assessment of API concentration, and the scattering properties could be linked to the matrix properties of the tablet, related to releasing properties of the API, including the delay and duration of the release after swallowing the tablet. These measurements could be complemented by NIR gas spectroscopy to further asses the matrix properties of the tablets [64,158,159,[162][163][164][165][166][167][168][169][170][171][172][173].…”

Diffuse photon remission associated with the center-illuminated–area-detection geometry. II. Approach to the time-domain model

“…Unlike in the steady-state measurement, time-domain DRS [11] can distinguish the temporal patterns between that caused by a change of the scattering-induced photon pathlength and that induced by a change of absorption over a scattering-determined pathlength. The potential of time-domain or time-of-flight (ToF) measurements to differentiate the effects on the diffuse reflectance between that caused by changes of absorption and scattering has made ToF DRS much more accurate and thus valuable to brain mapping [12], muscle monitoring [13], and noninvasive assessment of lipid [14], collagen [15], bone [16], food [17], wood [18], pharmaceuticals [19], and semiconductor powders [20], etc.…”

New frontiers in time-domain diffuse optics, a review

“…37 In these studies, the target was mainly oxygenated and deoxygenated blood content in biological tissues. The TD technique has been also used for the nondestructive optical characterization of food, 41 wood, 42 pharmaceuticals, [43][44][45] and semiconductor powders. The TD technique has been also used for the nondestructive optical characterization of food, 41 wood, 42 pharmaceuticals, [43][44][45] and semiconductor powders.…”