(572a) Thermoplastic Copolyesters: A Novel Solution for 3D-Printed, Implantable Drug Delivery Devices

In the last decade, individualized, patient-centered formulations have gained attention due to the emerging 3D-printing technologies [1]. One such technology is fused filament fabrication (FFF), which is currently mainly applied to oral formulations. Only a handful of studies have implemented FFF for non-biodegradable controlled-release drug-delivery devices (CDDD), mainly due to the poor printability of non-biodegradable, highly-elastic polymers such as ethylene-vinyl acetate (EVA) [2]. In this study, the 3D-printability of EVA9 (9% vinyl-acetate), EVA28 (28% vinyl-acetate) and a novel, non-biodegradable thermoplastic co-polyester (TPC) were compared for the first time. Furthermore, the drug-polymer interactions and drug-releasing properties of all polymers were investigated, using progesterone (P4) as a model drug. Finally, 3D-printed TPC-based urethra pessaries and implants were drug-loaded via impregnation and subjected to in-vitro drug-release studies. Compared to EVAs, the superior printability of TPC was a result of higher Young’s modulus, lower melt viscosity and lower polymer crystallinity. The P4/polymer solubility followed the order EVA9<EVA28<TPC and was attributed to the lower TPC crystallinity (11.8±0.8%) compared to EVA9 (33.3±1.4%) and EVA28 (20.8±0.4%). The P4 diffusivity was mainly influenced by the density of the amorphous regions, following the order TPC≤EVA9<EVA28 (Fig. 1a). Based on these results, the expected drug-release was calculated and compared to the experimental data. It was found that, on top of the superior printability, TPC showed very similar drug-release rates to EVA28 and was, therefore, chosen for further studies. Drug-loading of 3D-printed samples via impregnation resulted in preferential P4 distribution within the outer specimen layers. For the implants, this was translated in pharmacologically relevant and relative constant drug fractions released over time. For the pessaries, high burst release was observed owing to the larger diffusional path required for the P4 solution to reach the core of the geometry and due to process-induced changes in the overall porosity of the pessary (Fig. 1b). Although the impregnation procedure requires sample geometry-specific adaptations, the results suggested that TPC can deliver high and tunable release-rates of P4 via a 3D-printed non-biodegradable CDDD.

Figure caption

Figure 1: (a) Progesterone solubility and diffusivity in TPC and EVA polymers, (b) progesterone release from 3D-printed pessaries and implants

References

1. Mohammed, A.; Elshaer, A.; Sareh, P.; Elsayed, M.; Hassanin, H. Additive Manufacturing Technologies for Drug Delivery Applications. Int. J. Pharm. 2020, 580, 119245.
2. Genina, N.; Holländer, J.; Jukarainen, H.; Mäkilä, E.; Salonen, J.; Sandler, N. Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices. Eur. J. Pharm. Sci. 2016, 90, 53–63.