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

Qilei Zhang,Paolo Avalle,Lynn Gladden,Michael Mantle,J Zeitler

doi:10.3390/pharmaceutics5040591

Qilei Zhang, Paolo Avalle + Show 3 more

Open Access

https://doi.org/10.3390/pharmaceutics5040591

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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.

Highlights

Dosage form stability is an important aspect in the drug development processes
The unstressed tablet exhibited a slightly lighter color with sharp and clear embossed letters, whereas the stressed tablet had a rougher surface and blurred embossed letters. This is reflected in the coating thickness variation as measured by Figure 3 shows a typical time-domain terahertz waveform acquired via Terahertz pulsed imaging (TPI) measurements from an unstressed Lescolr XL tablet
The results shown in this study indicate that the direct exposure of the Lescolr XL tablet to the accelerated storage condition changed some coating properties, such as coating roughness and thickness

Summary

Introduction

Dosage form stability is an important aspect in the drug development processes. Accelerated stability testing allows manufacturers to establish recommended storage conditions and evaluate the shelf-life of products. For solid dosage forms, direct evidence of product stability is gathered using standard drug dissolution results Factors such as formulation components, processing and storage conditions can all influence the dissolution stability of tablets during storage. Krishnaiah et al [8] studied the stability of a controlled release tablet made of a three-layer guar gum matrix using high-performance liquid chromatography (HPLC) and differential scanning calorimetry (DSC) For this formulation no change in physical appearance, drug content or dissolution profile was found after storage at 40 ◦ C/75% r.h. Nafee et al [9] compared miconazole nitrate dosage forms (sustained release mucoadhensive patches) before and after aging using scanning electron microscopy and a two phase titration technique They found that the release rate of miconazole nitrate increased after being stored at 37 ◦ C/75% r.h. and this observation was linked to the change of the drug crystallinity: Nafee et al suggested that the drug crystals transformed into an amorphous state during the stressed storage period. The same effect was observed following recrystallization of the drug into a less soluble crystal structure [12]

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