Development of Flow-Through Cell Dissolution Method for In Situ Visualization of Dissolution Processes in Solid Dosage Forms Using X-ray μCT.

Abstract

Visualization of the dynamic behavior of pharmaceutical dosage forms during the dissolution process offers a better understanding of the drug release mechanism, enabling the design of customized dosage forms. In this study, an X-ray tomography-based approach is proposed to monitor and analyze the dynamics of the structure at the pore scale level during the dissolution process. A flow-through cell dissolution apparatus was developed, capable of mimicking the standard in vitro dissolution process, which can be easily positioned in an X-ray tomography setup. The method was utilized to study the dissolution of a Capa® (polycaprolactone)-based sustained-release 3D printed tablet. The impact of the flow rate on the active pharmaceutical ingredient (API) release rate was studied and 16 mL/min was selected as a suitable flow rate. Furthermore, cesium chloride (CsCl) was used as a contrast agent to increase the contrast between the sample and the dissolution medium. Data obtained with this novel technique were in a good agreement with the released drug rate acquired by the standard in vitro dissolution test (the similarity factor (f2) = 77%). Finally, the proposed approach allowed visualizing the internal structure of the sample, as well as real-time tracking of solution ingress into the product.