Intrauterine device, and a method of reducing the rate of diffusion of active ingredients in said intrauterine device
Inventors
KENDRUP, John Ingvar Feldtblad
Assignees
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Publication Number
US-11872284-B2
Publication Date
2024-01-16
Expiration Date
Abstract
An intrauterine device having at least one first pharmaceutically active ingredient and at least one first layer made of at least a first polymeric material, wherein between about 10 and about 60 v/v % of at least one particulate material is dispersed and/or incorporated in the first polymeric material. The presence of the particulate material will reduce the porosity of the polymer or otherwise obstruct the diffusion of the pharmaceutically active ingredient being released, thereby slowing its rate of release. In this way, it is possible to regulate the release rate and/or initial burst of the device, simply by adjusting the amount of particles/particulate material in the first layer, instead of having to adapt the size of the device to the desired release pattern, which requires expensive changes in production equipment and manufacturing processes.
Core Innovation
The invention relates to an intrauterine device that slows and regulates drug diffusion by using at least one first pharmaceutically active ingredient contained in a polymeric first layer with a dispersed particulate material. The particulate material is present in an amount of between 10 and 60 v/v % and obstructs diffusion of the pharmaceutically active ingredient being released to provide a zero order release profile.
The particulate material comprises inert three dimensional shapes with mean particle sizes between 3.6 µm and 100 µm. The particulate material forms a geometric structure with spaces therebetween, and molecules of the at least one active ingredient are contained within the spaces of the geometric structure between the shapes of particulate material.
The disclosure further characterizes particulate forms including plate like, flat, layered structures, and requires that particle thickness, height, or width is above 0.1 µm. The described particulate dispersions and polymer-layer architecture are presented as enabling reduced initial burst and substantially zero-order release, including multi-layer and gradient arrangements of particulate and actives.
Claims Coverage
The document provides three independent claim scopes, each directed to an intrauterine device with zero order release achieved by a polymeric first layer containing a diffusion-obstructing particulate at 10–60 v/v %. Across the independent claims, the inventive features are centered on the particulate volume fraction and role in obstructing diffusion, the particulate being inert three dimensional shapes forming a geometric structure with spaces that contain active ingredient molecules, and particle size and dimensional constraints that define the particulate morphology for the intended release behavior.
Diffusion-obstructing particulate in a polymeric first layer for zero order release
An intrauterine device comprising at least one first pharmaceutically active ingredient and at least one first layer made of at least a first polymeric material having dispersed therein between 10 and 60 v/v % of at least one particulate material that obstructs the diffusion of the pharmaceutically active ingredient being released and provides a zero order release of the active ingredient.
Inert three dimensional particulate shapes forming a geometric structure with spaces
The particulate material comprises three dimensional shapes that are inert and have mean particle sizes of between 3.6 µm and 100 µm, and the particulate material forms a geometric structure of the shapes with spaces therebetween, wherein molecules of the at least one active ingredient are contained within the spaces of the geometric structure between the shapes of particulate material.
Plate/flat/layered particulate morphology with thickness above 0.1 µm
The particulate material comprises three dimensional shapes that are inert and have mean particle sizes of between 3.6 µm and 100 µm, and wherein the particulate material forms a geometric structure of the shapes with spaces therebetween, wherein molecules of the at least one active ingredient are contained within the spaces of the geometric structure between the shapes of particulate material, and wherein said particles have a plate like structure, a flat structure and/or a layered structure and wherein the thickness of said particles are above 0.1 µm.
Particulate dimensional constraints above 0.1 µm in any dimension
The particulate material comprises three dimensional shapes that are inert and have mean particle sizes of between 3.6 µm and 100 µm, and the particulate material forms a geometric structure of the shapes with spaces therebetween, wherein molecules of the at least one active ingredient are contained within the spaces of the geometric structure between the shapes of particulate material, and wherein said particles have a thickness, height, and width which are above 0.1 µm in any of the three dimensions.
Across the independent claims, the inventive concept is to achieve zero order release in an intrauterine device by dispersing an inert particulate material (10–60 v/v %) within a polymeric first layer such that the particulate obstructs diffusion. The claims further require that inert three dimensional particles form a geometric structure with spaces containing active ingredient molecules, while imposing specific mean particle-size limits (3.6–100 µm) and particulate dimensional constraints (including thickness or thickness/height/width above 0.1 µm, and plate/flat/layered forms in one claim).
Stated Advantages
Provides zero order release and slows/regulates drug diffusion.
Reduces initial burst.
Enables substantially zero-order release with reduced initial burst behavior.
Reduced dose dumping and improved release characteristics are described.
Smaller size, reduced variability, improved manufacturability and shelf life are described.
Improved manufacturability and shelf life are described.
Documented Applications
In-vitro release evaluation for estradiol and ethinyl estradiol is documented, including day-1 burst and release-rate effects associated with talc particle size and concentration variants.
In-vitro release evaluation for drospirenone is documented, including comparison of talc versus sub-0.1 µm fumed silica and the effect on release behavior.
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