(81g) In-Line Skin Thickness Evaluation on Co-Extruded Vaginal Rings By Means of Optical Coherence Tomography

Hot-melt extrusion (HME) has been extensively used for the manufacturing of a wide array of drug delivery systems such as granules, tablets and implants. One specific type of HME process enables the manufacturing of multilayer systems such as core-membrane or ‘reservoir-type’ formulations. Such systems consist of a core containing the active pharmaceutical ingredient(s) (APIs) in a polymeric carrier and a drug-free membrane, which controls the permeation and release of the drug in the surrounding environment. This design results in a constant, zero-order release over long times, which, in turn, translates into high patient compliance. For a given system, i.e. API loading and types of polymers used, the main contribution to the drug release falls on the membrane thickness and the membrane homogeneity. Commonly, the membrane thickness of co-extrudates is evaluated offline via optical microscopy or µ-CT imaging of single cross-sectional cuts. However, both methodologies are associated with several drawbacks: in both cases, the assessment is time-consuming and not destruction free due to the required cuts or the exposure to ionizing radiation. Moreover, the results might not be representative of the extrusion process, since only fractions of a sample are investigated from a whole batch and manual cutting might induce additional changes in the membrane due to mechanical stress. Consequently, a fast, non-destructive and reproducible method to evaluate the membrane thickness of co-extruded reservoir systems is of great interest.

Our current study intends to address this gap by presenting an in-line capable, non-invasive methodology based on optical coherence tomography (OCT) to evaluate the membrane characteristics of ethylene-vinyl acetate (EVA) based co-extrudates, aiming at quicker but simultaneously more representative results. The presented approach opens the way to demonstrate the capabilities of OCT as an inline quality assurance tool for the manufacturing of the next generation of co-extruded formulations. OCT as a technology is well-known and established in the fields of medicine, art conservation, and non-destructive testing. Furthermore, RCPE has pioneered its use in pharmaceutical applications, specifically for real-time monitoring the coating thickness of solid dosage forms such as tablets and pellets. While measuring coating thickness and its uniformity is the basic functionality of pharmaceutical OCT systems, the potential of the approach is far greater. OCT is capable of detecting abrupt changes in material refractive index and scattering properties. Hence, it can visualize internal structures and morphology e.g., delamination and excipient agglomerates with sufficient size within the membrane structure.

In our talk, we will present an approach to use OCT as an in-line tool for co-extrusion processes. We will compare the results obtained by means of OCT and compare them to state of the art microscopic investigation of cross-sectional cuts. Aspects discussed will be advantages and disadvantages of both methods and obtained results. One considerable advantage of OCT is the real time capability, reporting instantaneous results. As such, the influence of the strand speed during extrusion was investigated as well in a range of 65 – 130 mm/sec. Investigations on extruded strands revealed one additional merit of using OCT, as details on the membrane joint, where the co-extruder provides the polymer melt generated some defects became obvious and quantifiable. In summary, we believe that the use of OCT as a process analytical technology in HME, and in particular co-extrusion processes, has the potential to act as a game changer. Reasons to believe so are the fast and destruction free measurements, the high resolution and wealth of information obtainable.