In-situ monitoring of in vitro drug release processes in tablets using optical coherence tomography.

ABSTRACT

Film-coated modified-release tablets are an important dosage form amenable to targeted, controlled, or delayed drug release in the specific region of the gastrointestinal (GI) tract. Depending on the film composition and interaction with the GI fluid, such coated products can modulate the local bioavailability, systemic absorption, protection as an enteric barrier, etc. Although the interaction of a dosage form with the surrounding dissolution medium is vital for the resulting release behavior, the underlying physicochemical phenomena at the film and core levels occurring during the drug release process have not yet been well described. In this work, we attempted to tackle this limitation by introducing a novel in vitro test based on optical coherence tomography (OCT) that allows an in-situ investigation of the sub-surface processes occurring during the drug release. Using a commercially available tablet based on osmotic-controlled release oral delivery systems (OROS), we demonstrated the performance of the presented prototype in terms of monitoring the membrane thickness and thickness variability, the surface roughness, the core swelling behavior, and the porosity of the core matrix throughout the in vitro drug release process from OROS. The superior spatial (micron scale) and temporal (less than 10 ms between the subsequent tomograms) resolution achieved in the proposed setup provides an improved understanding of the dynamics inside the microstructure at any given time during the dissolution procedure with the previously unattainable resolution, offering new opportunities for the design and testing of patient-centric dosage forms.