Coating and Density Distribution Analysis of Commercial Ciprofloxacin Hydrochloride Monohydrate Tablets by Terahertz Pulsed Spectroscopy and Imaging

Abstract

Terahertz pulsed spectroscopy was used to qualitatively detect ciprofloxacin hydrochloride monohydrate (CPFX·HCl·H2O) in tablets, and terahertz pulsed imaging (TPI) was used to scrutinize not only the coating state but also the density distribution of tablets produced by several manufacturers. TPI was also used to evaluate distinguishability among these tablets. The same waveform, which is a unique terahertz absorption spectrum derived from pure CPFX·HCl·H2O, was observed in all of the crushed tablets and in pure CPFX·HCl·H2O. TPI can provide information about the physical states of coated tablets. Information about the uniformity of parameters such as a coating thickness and density can be obtained. In this study, the authors investigated the coating thickness distributions of film-coated CPFX·HCl·H2O from four different manufacturers. Unique terahertz images of the density distributions in these commercial tablets were obtained. Moreover, B-scan (depth) images show the status of the coating layer in each tablet and the density map inside the tablets. These features would reflect differences resulting from different tablet-manufacturing processes.

Review of Terahertz Pulsed Imaging for Pharmaceutical Film Coating Analysis

“…This in turn provided information on the spatial and statistical distribution of coating thickness for a wide range of products such as film-coated tablets, sugar-coated tablets, multi-layered controlled release tablets and soft gelatin capsules ( Figure 2). For film coatings that protect the active ingredient against light and moisture, TPI has been applied to assess coating uniformity and density analysis [21].…”

“…The results of which were successfully validated against scanning electron microscopy (SEM), XµCT, acid uptake tests and loss on drying (LOD) test, a measure of water content in sample tablets. TEFPS was previously shown to reveal information on surface density and roughness [20,21] and it was further demonstrated in [32] how TEFPS could additionally provide information on the physical strength of the tablet surface for the estimation of surface defect risk. The ability to resolve air gaps in turn could provide information on adhesion quality between core and coatings in calendered tablets [33].…”

Spectroscopic Analysis of Melatonin in the Terahertz Frequency Range

“…Furthermore, an additional modality of systems allowing to perform THz imaging provides a visualization of individual chemical compounds within heterogeneous samples, such as pharmaceutical pellets. A THz imaging analytical method, known as component spatial pattern analysis [33], has been employed for chemical mapping of cocrystals [34] and for the determination of coating layer thickness and density [35]. Since plastics are almost transparent to THz waves, THz spectroscopic imaging can also reveal the distribution of both active pharmaceutical ingredient (API) and other important constituents within the pharmaceutical pellets covered by blisters.…”