Distributed Manufacturing: Personalization of 3DPrinted Intravaginal-Rings by Droplet Deposition Modeling

Intravaginal rings (IVRs) are drug-device combination delivery systems ‎designed for controlled drug release in vaginal cavity. Commercial ‎IVRs are based on the one-size-fits-all approach, where all the patients receive the same drug in similar doses and frequencies, allowing no space for tailored treatment per the patient’s needs. Moreover, the conventional manufacturing methods of IVRs, such as injection molding and hot-melt extrusion, face limitations in design flexibility and material capabilities due to their reliance on elevated temperatures and pressures. Additive manufacturing plays an essential role in the customization and flexibility of IVRs. Additive manufacturing offers an opportunity to overcome these limitations by providing the freedom of design, enabling enhanced control and tunability of IVRs characteristics such as size, shape, surface area, geometry, drug loading, drug combinations, and drug release properties. This presentation will highlight a comprehensive case study of integrating additive manufacturing, particularly Droplet Deposition Modeling (DDM), in distributed manufacturing settings for the personalization of IVRs. Three key aspects are explored: (1) the integration of patient-specific factors to unlock critical performance attributes essential for personalized IVR design, (2) the process of identifying an adaptable design space for IVR manufacturing through DDM, highlighting the technology's advantages such as design freedom, precise control over characteristics (e.g., size, shape, surface area), and the incorporation of tailored drug combinations and release properties, and (3) regulatory factors in adoption of 3D printing into distributed manufacturing settings.

The implementation of DDM includes optimizing various processing parameters, namely infill density, aspect ratio, and discharge percent, to ensure the desired properties and performance of IVRs. The results of this case study will demonstrate the significant impact of these parameters on the mechanical and drug release properties of 3D printed IVRs. For example, increased infill density and discharge percent increased IVR properties such as weight, shore hardness, compression strength, Young’s modulus, storage and loss modulus, and drug release rate of the IVRs. Conversely, aspect ratio exhibited an opposite effect in these IVRs properties. The Higuchi kinetic model demonstrated a diffusion-controlled mechanism in IVRs, with formulation showing drug release rate ranging from 0.11 ± 0.01 to 0.24 ± 0.02 mg/day0.5. Internal geometry of IVR was investigated by MicroCT analysis to correlate the microstructure characteristic to the performance of each individual batch of IVRs. In summary, this presentation highlights the potential of DDM in 3D printing process for IVR manufacturing, emphasizing the importance of integrating patient-specific factors for personalized IVRs. Furthermore, the regulatory considerations and landscape crucial for the widespread adoption of additive manufacturing in IVR production are discussed.