Design and Characterization of a Novel Series of Geometrically Complex Intravaginal Rings with Digital Light Synthesis

Abstract

Intravaginal rings (IVRs) represent a sustained‐release approach to drug delivery and have long been used and investigated for hormones and microbicides delivery. For decades, IVRs have been manufactured by injection molding and hot‐melt extrusion with very limited design and material capabilities. Additive manufacturing (AM), specifically digital light synthesis (DLS), represents an opportunity to harness the freedom of design to expand control and tunability of drug release properties from IVRs. A novel approach to IVR design and manufacturing is reported that results in geometrically complex internal architectures through the incorporation of distinct unit cells using computationally aided design (CAD) software. A systematic approach is developed to design through the generation of an IVR library and the effects of these parameters are investigated on ring properties. The ability to precisely and predictably control the compressive properties of the IVR independent of the internal architecture with which control of drug release kinetics can be achieved is demonstrated, thus opening the door for a “plug‐and‐play” platform approach to IVR fabrication.

Multipurpose Prevention Technologies: Oral, Parenteral, and Vaginal Dosage Forms for Prevention of HIV/STIs and Unplanned Pregnancy

“…Additive manufacturing (3D printing) offers an opportunity to further improve upon IVR fabrication by expanding IVR design scope, thus allowing for greater control on drug release kinetics and the ability to achieve complete drug release from the IVR. To our knowledge, all MPT IVRs in development incorporate standard injection molding techniques to some extent, and there are only three published attempts to 3D print IVRs [ 127 , 128 , 129 ] based on an extensive literature search. For instance, Fu et al demonstrated one of the first attempts to 3D print an IVR for the contraceptive delivery of progesterone [ 127 ].…”

“…More recently, Janusziewicz et al reported on 3D-printed IVRs fabricated using digital light synthesis or continuous liquid interface production (CLIP™) [ 129 , 130 ]. This method utilizes a photosensitive resin that selectively solidifies upon exposure to ultra-violet (UV) light via free radical photopolymerization mechanisms to generate the final product [ 130 ].…”

“…This allows for continuous production of monolithic parts with smooth, nonlayered, and high-resolution structures at print rates upwards of 100 mm/hr. Janusziewicz et al developed a design library of geometrically complex biocompatible silicone polyurethane-based IVRs, compared their mechanical properties to commercial rings (NuvaRing ® and Estring ® ), and assessed the fidelity of the CLIP-fabricated IVR to the original CAD file [ 129 ]. Incorporating geometric complexity to IVRs eliminates its solid crosssection and has the potential to promote targeted release kinetics and complete drug release as drug diffusion distance can be controlled.…”

“…Although CLIP has many advantages for developing 3D-printed IVRs, there are still limitations. For example, after printing, the silicone polyurethane IVRs require an 8 h and 120 °C postthermal cure step [ 129 ], which can degrade APIs that are sensitive to high heat if the drug is incorporated in the resin during printing. Additionally, UV exposure is a critical component of the CLIP IVR fabrication process, which limits API options that are sensitive to UV light if incorporating the drug into the resin.…”

3D Printed Punctal Plugs for Controlled Ocular Drug Delivery

“…In addition, it operates at room temperature; hence, it avoids the risk of thermal degradation of drugs [ 50 ]. Thus far, vat photopolymerisation 3D printing techniques have been explored to prepare pharmaceutical products for various drug delivery purposes, including oral dosage forms [ 51 , 52 , 53 ], nose patches [ 45 ], microneedles [ 54 , 55 , 56 ], intravaginal rings [ 57 ], dental [ 58 ], bladder devices [ 59 ] and hearing aids [ 60 ].…”