US-12616823-B2 - Sustained release formulations in delivery devices

Abstract

An intra-ruminal device includes a body substantially impervious to rumen fluid, the body including a barrel, at least one outlet, at least one matrix including at least one active ingredient and at least one clay mineral, a compression arrangement and at least one variable geometry device dependent from the body. Use of the intra-ruminal device and a method of treating a ruminant animal by administering the intra-ruminal device to the animal are also disclosed.

Inventors

• David Anthony Gill
• Desmond Ian John Morrow
• Michael Venning

Assignees

• ARGENTA INNOVATION LIMITED

Dates

Publication Date

20260505

Application Date

20190910

Priority Date

20180910

Claims (20)

1. 1 . An intra-ruminal device comprising a body substantially impervious to rumen fluid, the body comprising a barrel, at least one outlet, and at least one matrix in the barrel, a compression arrangement within the body adapted to bias the at least one matrix in the barrel to the at least one outlet, and at least one variable geometry device dependent from the body to assist rumen retention; wherein the at least one matrix in the barrel comprises at least one active ingredient, 5% to 50% by weight of a gel former comprising a sucrose fatty acid ester, and 5% to 40% by weight of at least one clay mineral; and wherein the device is configured to provide a sustained delivery of the one or more active ingredients over a period greater than 150 days.
2. 2 . The intra-ruminal device of claim 1 , wherein the clay mineral is selected from the group consisting of kaolin, talc, nontronite, saponite, sepiolite, palygorskite, halloysite, vermiculite, muscovite, illite, hectorite, montmorillonite, bentonite, beidellite, volkonskoite, laponite, sauconite, magadiite, kanyaite, ledikite, nacrite, attapulgite, or zeolite, or a combination thereof.
3. 3 . The intra-ruminal device of claim 1 , wherein the clay mineral is kaolin.
4. 4 . The intra-ruminal device of claim 1 , wherein the device provides sustained delivery of the one or more active ingredients over at least 250 days.
5. 5 . The intra-ruminal device of claim 4 , wherein the sustained delivery is linear with a linearity value of >0.95.
6. 6 . The intra-ruminal device of claim 1 , wherein the device provides sustained delivery of the one or more active ingredients over at least 300 days.
7. 7 . The intra-ruminal device of claim 6 , wherein the sustained delivery is linear with a linearity value of >0.95.
8. 8 . The intra-ruminal device of claim 1 , wherein the compression arrangement within the body is adapted to bias the at least one matrix in the barrel to the at least one outlet at a rate of 0.1 mm to 1.2 mm per day.
9. 9 . The intra-ruminal device of claim 1 , wherein the compression arrangement within the body is adapted to bias the at least one matrix in the barrel to the at least one outlet at a rate of 0.1 mm to 0.8 mm per day.
10. 10 . The intra-ruminal device of claim 1 , wherein the compression arrangement within the body is adapted to bias the at least one matrix in the barrel to the at least one outlet at a rate of 0.2 mm to 0.6 mm per day.
11. 11 . The intra-ruminal device of claim 1 , wherein the at least one active ingredient is selected from the group consisting of parasiticides, non-steroidal anti-inflammatories, antibiotics, probiotics, antivirals, anthelmintics, steroid hormones, metabolic regulators, enzyme inhibitor, rumen methane inhibitors/regulators, ruminal fermentation modifiers, productivity regulators, vitamins and minerals, or a combination thereof.
12. 12 . The intra-ruminal device according to claim 1 , wherein the at least one active ingredient is a parasiticide.
13. 13 . The intra-ruminal device of claim 12 , wherein the parasiticide is an anthelmintic selected from the group consisting of benzimidazoles, imidazothiazoles, tetrahydropyrimidines, macrocyclic lactones, salicylanides, substituted phenols, aromatic amides, isoquinolines, amino acetonitriles and spiroindoles, or a combination thereof.
14. 14 . A method of assembling a controlled delivery intra-ruminal device according to claim 1 , the method comprising a) granulating a mixture comprising at least one active ingredient, 5% to 50% by weight of a gel former comprising a sucrose fatty acid ester, and 5% to 40% by weight of at least one clay mineral, b) drying the granules, c) passing the granules through a sieve, and d) tabletting the granules into at least one matrix, and e) loading the at least one matrix into the body of an intra-ruminal device.
15. 15 . The method of claim 14 , wherein the mixture further comprises one or more excipients.
16. 16 . The intra-ruminal device of claim 1 , wherein the sustained delivery is linear with a linearity value of >0.95.
17. 17 . The intra-ruminal device of claim 1 , wherein the compression arrangement within the body is adapted to bias the at least one matrix in the barrel to the at least one outlet at a rate of 0.1 mm to 1.2 mm per day.
18. 18 . The intra-ruminal device of claim 1 , wherein the compression arrangement within the body is adapted to bias the at least one matrix in the barrel to the at least one outlet at a rate of 0.1 mm to 0.8 mm per day.
19. 19 . The intra-ruminal device of claim 1 , wherein the compression arrangement within the body is adapted to bias the at least one matrix in the barrel to the at least one outlet at a rate of 0.2 mm to 0.6 mm per day.
20. 20 . The intra-ruminal device of claim 1 , wherein the gel former is present at 20% to 50% by weight.

Description

FIELD OF THE INVENTION The present invention relates to an intra-ruminal device comprising a formulation that allows for sustained, controlled delivery of one or more active therapeutic ingredients to a ruminant animal. BACKGROUND TO THE INVENTION The delivery of pharmaceutically active ingredients or other substances to an animal in a sustained and controlled manner is desirable. Various devices and methods to deliver active ingredients to ruminants are known in the art. However, a number of these continue to be limited by their. inability to effectively control the delivery rate of a therapeutic agent over an extended period of time, and/or.limited payout duration, and/orability to maintain a reproducible dose-rate due to, for example, variability in delivery rate and/or product failure. Such problems may lead to potential toxicity from over-dosing or poor efficacy from under-dosing. Sub-therapeutic levels of certain therapeutics such as anti-parasitic or anti-microbial products may lead to other problems, for example, the development of drug resistant micro-organisms. Existing sustained release technologies for the oral delivery of therapeutics to ruminants have limited duration of up to approximately 150 days. Extending the release period from a device may be beneficial for the delivery of selected actives where a single application could replace multiple applications, thereby reducing the number of associated dosage breaks, and/or.the potential for peaks and troughs in the therapeutic period, and/orreducing the cost of treatment. Providing substantial increases in the sustained release period without compromising linearity of dose in a device that maintains an acceptable size for oral delivery may also have significant benefits for managing animal health and end user compliance Extending the sustained release period from an intra-ruminal device using existing technology may result in increased variability of delivery or, in extreme cases, failure of the device function, for example, failure of the piston to move effectively at very low speed. There is a need for intra-ruminal devices that allow for the sustained delivery of one or more actives to ruminant animals. It is an object of the present invention to go some way to meeting this need; and/or to at least provide the public with a useful choice. SUMMARY OF THE INVENTION In a first aspect the present invention may be said to broadly relate to an intra-ruminal device comprising a body substantially impervious to rumen fluid, the body comprising a barrel, at least one outlet, and at least one matrix in the barrel,a compression arrangement within the body adapted to bias the at least one matrix in the barrel to the at least one outlet, andat least one variable geometry device dependent from the body to assist rumen retention,wherein the at least one matrix in the barrel comprises at least one active ingredient and at least one clay mineral. In a further aspect the present invention relates to a method of treating a ruminant animal in need thereof the method comprising administering the intra-ruminal device of the invention to a ruminant animal. In a further aspect the present invention relates to a controlled delivery intra-ruminal device according to any one of claims 1 to 16, the method comprising granulating a mixture comprising at least one active ingredients, at least one clay mineral, and optionally one or more excipients,drying the granules,passing the granules through a sieve, andtabletting the granules into at least one matrix, andloading the at least one matrix into the body of an intra-ruminal device. Preferably the device delivers an effective concentration of at least one active ingredient to a ruminant in need thereof. Preferably the clay mineral is selected from the group consisting of kaolin, talc, nontronite, saponite, sepiolite, palygorskite, halloysite, vermiculite, muscovite, illite, hectorite, montmorillonite, bentonite, beidellite, volkonskoite, laponite, sauconite, magadiite, kanyaite, ledikite, nacrite, attapulgite, or zeolite, or a combination thereof. Preferably the clay mineral is kaolin. Preferably the clay mineral is present in an amount of 5-40% by weight of the matrix. Preferably the device is for use in a method of treating a ruminant animal. Preferably the device provides a sustained delivery of the one or more active ingredients over at least about 150 days. Preferably the device provides a sustained delivery of the one or more active ingredients over at least about 250 days. Preferably the device provides a sustained delivery of the one or more active ingredients over at least about 300 days. Preferably the sustained delivery is substantially linear (>0.95). Preferably the compression arrangement within the body is adapted to bias the at least one matrix in the barrel to the at least one outlet at a rate of about 0.1 to about 1.2 mm per day. Preferably the compression arrangement within the body is adapted to bias the