(372a) Novel Vaginal Pessary Platform Via 3D-Printing: Concomitant Mechanical Support and Drug Delivery

Currently, pessaries are removeable, drug-free polymeric structures that are inserted into the vagina to support the pelvic organs, including the urethra, the bladder and the uterus. They are used to treat urinary incontinence, especially stress urinary incontinence, which affects more than 40% of women worldwide (1). Although pessaries offer great advantages, such as easy self-administration and immediate relief of symptoms (namely involuntary urine loss) (2), they are not associated with great patient adherence (3). This is mainly due to the fact that commercial pessaries are made of silicon via injection molding and are thus, available only in a few sizes and shapes. We just recently showed that 3D-printing, more specifically material extrusion-based additive manufacturing, is an emerging manufacturing technique that circumvents these hurdles and allows for pessary personalization (4). In a subsequent process step, selected 3D-printed pessaries were loaded with drug via immersion (5). In an attempt to avoid issues associated with immersion processes, including non-uniform drug distribution, non-reproducible drug content and the application of organic solvents, we report the direct manufacturing of personalized, drug-loaded pessaries – particularly, incontinence rings – via a combination of filament extrusion and 3D-printing for the first time. Thereby, not only mechanical support but also a concomitant pharmacological therapy is provided, yielding a new generation of pessaries. Thermoplastic polyurethanes (TPUs) of different grades (varying hardness and hydrophobicity) served as polymeric carriers. In a first step, drug-free incontinence rings were prepared and tested for their mechanical characteristics. Both, the maximum compression force at a given deformation – which is a measure for the extent of mechanical support the incontinence ring provides in the vaginal cavity – and the component compression stiffness - indicating how easily the incontinence ring can be compressed for manual self-insertion into the vagina - were a function of i) the TPU grade, ii) the cross-sectional diameter and iii) the infill. For a set cross-sectional diameter (i.e., 7 mm), infills (i.e., 10-100%) were identified for each TPU grade to achieve favorable mechanical characteristics. In a second step, these parameters were applied to 3D-print incontinence rings comprising 10 wt.% of the model drug acyclovir (ACV). After 3D-printing, the ACV solid state was affected by the TPU grade (due to different hydrophobicities) and/or the nozzle temperature. Clearly, the in-vitro drug release properties were influenced by the drug solid state. However, the key factors to trigger the in-vitro ACV release from the 3D-printed incontinence rings – including the amount of ACV released per time unit, the duration of ACV release, and the release mechanism – were the interaction of the TPU polymer with the dissolution medium (swelling capacity) and the infill (interior porosity). Summarizing, our results demonstrate that TPU is a suitable polymer to build – together with 3D-printing – the platform for novel drug-loaded pessaries. The critical quality attributes of the novel pessary product, namely the mechanical properties and the in-vitro drug release characteristics are, however, not limited to the polymer material properties. Instead, the 3D-printing process allows for their adjustment within a broad range, which is the basis for personalized drug products.

References

1. Reynolds WS, Dmochowski RR, Penson DF. Epidemiology of stress urinary incontinence in women. Curr Urol Rep. 2011;12(5):370–6.
2. Al-Shaikh G, Syed S, Osman S, Bogis A, Al-Badr A. Pessary use in stress urinary incontinence: a review of advantages, complications, patient satisfaction, and quality of life. Int J Womens Health. 2018;10:195–201.
3. Jones KA, Harmanli O. Pessary Use in Pelvic Organ Prolapse and Urinary Incontinence. Rev Obstet Gynecol. 2010;3(1):3–9.
4. Spörk M, Arbeiter F, Koutsamanis I, Cajner H, Katschnig M, Eder S. Personalised urethra pessaries prepared by material extrusion-based additive manufacturing. In preparation.
5. Koutsamanis I, Paudel A, Alva Zúñiga CP, Wiltschko L, Spoerk M. Novel 3D-printed thermoplastic copolyesters for implantable drug delivery applications. In preparation.