Effect of density on dapivirine release from thermoplastic vaginal rings fabricated by additive manufacturing

Background: Droplet deposition modelling (DDM) is an additive manufacturing (AM) process employed by the Arburg Freeformer. A piezo controlled shut-off nozzle is used to discreetly control the exiting of material from the nozzle, creating polymeric droplets of defined geometry, providing precise levels of control over an object’s design and morphology. Properties including density, geometry and surface area can be manipulated in ways that cannot be achieved using conventional thermoplastic processing techniques. Here, the DDM process and injection moulding were used to manufacture dapivirine (DPV) loaded vaginal rings using a pharmaceutically relevant, life science grade thermoplastic polyurethane.

Methods: Vaginal rings (outer diameter 54.0 mm, cross sectional diameter 4.0 mm) were manufactured by injection molding or Arburg Plastic Freeforming – a proprietary DDM process, using a hydrophobic TPU (T87 or T60) loaded with 10% w/w dapivirine. Using the DDM process, rings of 100, 50 and 10% matrix density were produced. Rings were evaluated for in vitro drug release over 29 days in an aqueous release media and assessed for thermal characteristics.

Results: Raw materials were thermally stable with a weight loss (%) equal to or less than 0.70% at the maximum processing temperature. DSC thermal traces for TPU plus 10% w/w DPV showed that the DPV melt endotherm was absent, suggesting that it was fully solubilised within the TPU at the experimental conditions. Daily DPV release from all ring designs ranged between 387 - 8666 µg (Day 1) and 193 - 992 µg on Day 29. T87 and T60 DDM printed vaginal rings with 10% infill density (62 and 68 mg DPV load respectively) exhibited up to a seven fold increase in DPV release rate compared to injection moulded rings containing 192 mg DPV. For DDM printed rings, there was very significant correlation between decreasing ring density and increasing DPV release rate as a percentage of total drug loading.

Conclusions: Vaginal rings with an infill density of 100% manufactured by IM and DDM released up to 4 and 10% of their total DPV loading, while rings with an infill density of 50 or 10% (DDM) released up to 56 and 79% of their total DPV loading after 29 days. DDM printing on an Arburg Freeformer has therefore provided a new potential to either increase the release rate of poorly water soluble compounds or reduce the loading required to maintain a desired release rate.