Geometrically complex intravaginal rings, systems and methods of making the same

Patent metadata

Field	Value
Publication number	US-11219595-B2
Application number	US-201816139481-A
Country	US
Kind code	B2
Filing date	Sep 24, 2018
Priority date	Mar 23, 2016
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

Geometrically complex intravaginal rings, systems and methods of making the same are provided herein. Disclosed herein are geometrically complex intravaginal rings with tunable and enhanced drug release, which in some embodiments can be fabricated by 3D printing technologies. The disclosed IVRs include a ring structure comprising a plurality of unit cells or macroscopic and/or microscopic architecture, which can be tuned to control the loading capacity of an active compound within the IVR, the diffusion of an active compound from the IVR, the surface area of the IVR, and/or the mechanical properties of the IVR. The disclosed geometrically complex IVRs can provide superior control over drug loading and drug release compared to conventional IVRs fabricated by injection molding or hot-melt extrusion.

First claim

What is claimed is:

1. A geometrically complex intravaginal ring (IVR), the IVR comprising:
a three dimensional ring structure comprising a body forming an inner diameter and an outer diameter;
a plurality of unit cells, each of the unit cells comprising a macroscopic and/or microscopic architecture, wherein each of the unit cells forms a geometric shape, wherein the plurality of unit cells together form the body of the ring structure, wherein the IVR comprises one or more types of unit cells, wherein each type of unit cell varies in size, shape, configuration, surface area and/or three dimensional geometry;
a void volume that is regularly or irregularly distributed continuously or in discrete volumes amongst the plurality of unit cells, wherein the void volume is greater than or equal to about 10; and
an active compound;
wherein the macroscopic architecture and/or microscopic architecture of the unit cells is configured to control a loading capacity of the active compound within or on the IVR, a diffusion rate of the active compound from the IVR, a surface area of the IVR, a fractional volume of the IVR, and/or a mechanical property of the IVR.

2. The geometrically complex IVR of claim 1 , wherein a fractional volume of the IVR is about 0.1 to about 0.9, wherein the fractional volume is calculated based on Equation 2:
Volume Fraction×Loading   Equation 2

wherein the Volume Fraction is calculated based on Equation 1:

Geometric
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Complexity
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by
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Volume
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Fraction
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:

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Volume
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of
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IVR
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with
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Void
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Spaces

Volume
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of
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Solid
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IVR

<
1.

Equation
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1

3. The geometrically complex IVR of claim 1 , wherein the outer diameter, inner diameter, and/or a cross-section of the IVR can vary throughout the three dimensional ring structure.

4. The geometrically complex IVR of claim 1 , wherein a shape, size, and/or surface area of the IVR is fabricated by 3D printing; and
wherein the active compound is incorporated into the IVR during or after 3D printing.

5. The geometrically complex IVR of claim 4 , wherein the 3D printing used in fabrication comprises continuous liquid interface production (CLIP).

6. The geometrically complex IVR of claim 4 , wherein the active compound is incorporated into the IVR after 3D printing by coating, absorption, infusion, or adsorption of active compound onto the IVR.

7. The geometrically complex IVR of claim 4 , further comprising providing a gel-like compound, wherein the gel-like compound is incorporated into the IVR after 3D printing by filling a void volume of the IVR.

8. The geometrically complex IVR of claim 1 , wherein the active compound is captured inside one or more nanoparticles incorporated into the IVR.

9. The geometrically complex IVR of claim 1 , wherein a shape, size, and/or surface area of the IVR is produced by a foaming method or by a die-cut method.

10. The geometrically complex IVR of any of claim 1 , wherein the IVR is configured to control the rate and/or duration of diffusion of the active compound from the IVR, wherein the active compound is released from the IVR for an extended period of time, optionally 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 days or more.

11. The geometrically complex IVR of claim 1 , wherein the active compound comprises a therapeutic compound selected from an antiviral, antiretroviral, microbicide, contraceptive, antibiotic, hormone, pre-exposure prophylaxis, small molecule drug, macromolecule drug, biopharmaceutical, biologics, chemotherapeutic, other pharmaceutical compound, and combinations thereof.

12. The geometrically complex IVR of claim 1 , further comprising an additive selected from the group consisting of a pore-forming agent, a plasticizer, a stabilizer, a filler and combinations thereof, wherein the pore-forming agent comprises one or more of PEG 3000, PEG 6000, PEG 8000, hydroxypropyl cellulose, PVP 10000 , and PVA 10000 , wherein the pore-forming agent is configured to create aqueous diffusion pathways for a drug molecule over time.

13. The geometrically complex IVR of claim 1 , wherein the plurality of unit cells comprise a resin formulation, wherein the resin formulation comprises additives configured to influence drug solubility, viscosity, porosity, stability, or mechanical properties of the IVR during processing, or configured to influence surface properties, swelling, stability, or mechanical properties during packaging, storage, or use.

14. The geometrically complex IVR of claim 1 , wherein the IVR is configured to release two or more active compounds simultaneously or iteratively and a

Assignees

• Univ North Carolina Chapel Hill

Inventors

• Benhabbour Soumya Rahima
• Janusziewicz Rima
• Mecham Sue J

Classifications

• B33Y70/00

  Materials specially adapted for additive manufacturing · CPC title

• A61M31/00

  Devices for introducing or retaining media, e.g. remedies, in cavities of the body (A61M25/00 takes precedence {; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008}) · CPC title

• B29C64/124

  using layers of liquid which are selectively solidified · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• B29K2995/0093

  hydrophobic · CPC title