Evaluation of drug delivery profiles in geometric three-layered tablets with various mechanical properties, in vitro–in vivo drug release, and Raman imaging

Abstract

Even though various multi-layered tablets have been developed for sustained release formulations, evaluations of mechanical properties during dissolution with drug release and imaging in the tablets have been limited. A novel geometric system consisting of an inner immediate release layer and two extended release barrier layers with swellable hydrophilic polymers was suggested as a once-a-day formulation. To evaluate drug release mechanisms with geometric properties, various mechanical characteristics during swelling were investigated to comprehend the relationship among in vitro drug release, human pharmacokinetics, and geometric characteristics. Imaging of drug movement was also studied in real-time using Raman spectroscopy. Drug delivery in the tablets might be divided into three processes through the geometric properties. When exposed to aqueous environments, the drug in the mid-layer was released until wrapped by the swollen barrier layers. Then, the drug in the mid-layer was mainly delivered to the barrier layers and a small amount of the drug was delivered to the contact region of the swollen barrier layers. Finally, the delivered drug to the barrier layers was consistently released out in response to the characteristics of the polymer of the barrier layers. Using Raman spectroscopy, these processes were confirmed in real-time analysis. Moreover, in vitro drug release profiles and human pharmacokinetics showed consistent results suggesting that drug release might be dependent on the various geometric properties and be modified consistently during the formulation development.