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

Pharmaceutics

Qilei Zhang¹  Lynn F. Gladden³  Paolo Avalle²  J. Axel Zeitler³ 

[1] Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China; E-Mail:;Merck Sharp & Dohme Ltd., Hoddesdon EN11 9BU, UK; E-Mail:;Department of Chemical Engineering & Biotechnology, University of Cambridge, Cambridge CB2 3RA, UK; E-Mails:

关键词: magnetic resonance imaging;    terahertz pulsed imaging;    formulation stability;    drug release;    controlled release;   

DOI  :  10.3390/pharmaceutics5040591

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.