Terahertz Pulsed Imaging and Magnetic Resonance Imaging as Tools to Probe Formulation Stability

Abstract

Dissolution stability over the entire shelf life duration is of critical importance to ensure the quality of solid dosage forms. Changes in the drug release profile during storage may affect the bioavailability of drug products. This study investigated the stability of a commercial tablet (Lescol® XL) when stored under accelerated conditions (40 °C/75% r.h.). Terahertz pulsed imaging (TPI) was used to investigate the structure of the tablet coating before and after the accelerated aging process. The results indicate that the coating was reduced in thickness and exhibited a higher density after being stored under accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI) of the water penetration processes during tablet dissolution in a USP-IV dissolution cell equipped with an in-line UV-vis analyzer was carried out to study local differences in water uptake into the tablet matrix between the stressed and unstressed state. The drug release profiles of the Lescol® XL tablet before and after the accelerated storage stability testing were compared using a “difference” factor f1 and a “similarity” factor f2. The results reveal that even though the physical properties of the coating layers changed significantly during the stress testing, the coating protected the tablet matrix and the densification of the coating polymer had no adverse effect on the drug release performance.

Diffusion and Swelling Measurements in Pharmaceutical Powder Compacts Using Terahertz Pulsed Imaging

“…The developing gel layer acts as a diffusion barrier that slows down further water uptake and in turn alters the swelling kinetics of the tablet 9. Further, MRI studies have also investigated this effect in commercial products that use HPMC as a swellable matrix former 10,11. In contrast to the nondestructive MRI analysis, a range of destructive methods have been used to analyze the dissolution process in HPMC matrices including thermo gravimetric analysis,12,13 near-infrared (NIR) spectroscopy, and infrared imaging,14–16 among other techniques.…”

“…The theoretical models discussed above were developed and refined based on experimental data from MRI,4,7,11,25 NIR imaging,26 infrared imaging,15,16 and spectroscopy27 as well as other analytical tools. Terahertz imaging is a relatively recent technique for pharmaceutical analysis.…”

“…It has also been used to measure the surface density of uncoated tablets as well as tablet hardness 33. Previous research has demonstrated how MRI and TPI can be combined to quantify coating stability before and after accelerated storage conditions, and how changes in the coating stability affect the dissolution process 11. Here, we demonstrate that TPI can be used in a different context to resolve the penetration of water into a tablet with time, while simultaneously following how the dimensions of the tablet change.…”

“…24 Anomalous diffusion is a mode of transport that contains both Fickian and case II characteristics, this mode of transport is also described using the power law. 22 The theoretical models discussed above were developed and refined based on experimental data from MRI, 4,7,11,25 NIR imaging, 26 infrared imaging, 15,16 and spectroscopy 27 as well as other analytical tools. Terahertz imaging is a relatively recent technique for pharmaceutical analysis.…”

Contrast in Terahertz Images of Archival Documents—Part II: Influence of Topographic Features

“…Terahertz time-domain imaging can detect differences in the time of arrival to the detector due to variations in surface height of a measured sample. It can therefore be used to inspect, in a non-invasive way, the topography of the surface of an object, as well as the topography of layers within objects [2][3][4][5]. Well-contrasted terahertz images of a text written using ink with optical properties similar to that of the support might therefore be obtained by using information related to indentations in the support left by the writing tool that is imparted on the terahertz time-domain waveforms reflected from the surface.…”