Components with high API loading

Patent metadata

Field	Value
Publication number	US-11311489-B2
Application number	US-201816614172-A
Country	US
Kind code	B2
Filing date	May 17, 2018
Priority date	May 17, 2017
Publication date	Apr 26, 2022
Grant date	Apr 26, 2022

Abstract

Components with relatively high loading of active pharmaceutical ingredients are generally provided. In some embodiments, the component (e.g., a tissue interfacing component) comprises a solid therapeutic agent and a supporting material such that the solid therapeutic agent is present in the component in an amount of greater than or equal to 10 wt % versus the total weight of the tissue interfacing component. Such tissue-interfacing components may be useful for delivery of API doses e.g., to a subject. Advantageously, in some embodiments, the reduction of volume required to deliver the required API dose as compared to a liquid formulation permits the creation of solid needle delivery systems for a wide variety of drugs in a variety of places/tissues (e.g., tongue, GI mucosal tissue, skin) and/or reduces and/or eliminates the application of an external force in order to inject a drug solution through the small opening in the needle. In some cases, a physiologically relevant dose may be present in a single tissue interfacing component.

First claim

What is claimed is:

1. An article, comprising:
a tissue interfacing component,
the tissue interfacing component comprising a solid therapeutic agent and a supporting material,
wherein the article comprises an external surface having a monostatic shape and/or the center of mass of the article is configured such that the article has a single stable resting position,
wherein the solid therapeutic agent is present in the tissue interfacing component in an amount of greater than or equal to 10 wt % as a function of the total weight of the tissue interfacing component,
wherein the solid therapeutic agent and supporting material are distributed substantially homogeneously,
wherein the tissue interfacing component has a Young's elastic modulus of greater than or equal to 100 MPa, and
wherein the tissue interfacing component is configured to penetrate at least 1 mm into human gastrointestinal mucosal tissue with a force of less than or equal to 20 mN.

2. The article of claim 1 , wherein the tissue interfacing component comprises a plurality of microneedles comprising the solid therapeutic agent and the supporting material.

3. The article of claim 1 , wherein the tissue interfacing component comprises a supporting material associated with the tissue interfacing component.

4. The article of claim 1 , wherein the tissue interfacing component does not comprise a coating.

5. A method of forming an article comprising a tissue interfacing component, comprising:
providing a solid therapeutic agent and a supporting material;
compressing, using at least 1 MPa of pressure, and/or heating the solid therapeutic agent and a supporting material together to form the tissue interfacing component;
and associating the tissue interfacing component with the article, wherein the article comprises an external surface having a monostatic shape and/or the center of mass of the article is configured such that the article has a single stable resting position,
wherein the tissue interfacing component comprises greater than or equal to 10 wt % the solid therapeutic agent versus the total tissue interfacing component weight,
wherein the tissue interfacing component has a Young's elastic modulus of greater than or equal to 100 MPa, and
wherein the tissue interfacing component is configured to penetrate at least 1 mm into human gastrointestinal mucosal tissue with a force of less than or equal to 20 mN.

6. The method of claim 5 , wherein the compressing comprises centrifugation of the solid therapeutic agent and the supporting material.

7. The method of claim 5 , wherein the compressing comprises using at least 20 MPa of pressure.

8. The article of claim 1 , wherein the supporting material is biodegradable.

9. The article of claim 1 , wherein the supporting material comprises a polymer.

10. The article of claim 9 , wherein the polymer is selected from the group consisting of polyethylene glycol and HPMC.

11. The article of claim 1 , wherein the solid therapeutic agent is selected from the group consisting of active pharmaceutical ingredients, insulin, nucleic acids, peptides, and antibodies.

12. The article of claim 1 , wherein the tissue interfacing component comprises a coating.

13. The article of claim 1 , wherein the coating has a yield strength of greater than or equal to 50 MPa.

14. An article, comprising:
a tissue interfacing component comprising greater than or equal to 10 wt % solid active pharmaceutical agent versus the total tissue interfacing component weight,
wherein the tissue interfacing component has a Young's elastic modulus of greater than or equal to 100 MPa, and
wherein the tissue interfacing component is configured to penetrate at least 1 mm into human gastrointestinal mucosal tissue with a force of less than or equal to 20 mN
wherein the article has an external surface comprising a monostatic shape and/or the center of mass of the article is configured such that the article has a single stable resting position.

15. The article of claim 14 , wherein the active pharmaceutical agent is cast into a mold to form the article.

16. The article of claim 14 , further comprising a binder.

17. The article of claim 16 , wherein the binder comprises sugar such as sorbitol or sucrose, gelatin, polymer such as PVA, PEG, PCL, PVA or PVP, and/or ethanol.

18. The article of claim 14 , wherein the article comprises greater than or equal to 1 mg of active pharmaceutical agent.

19. The article of claim 14 , wherein the active pharmaceutical agent is selected from the group consisting of bacteriophage, DNA, insulin, human growth hormone, monoclonal antibodies, adalimumab, epinephrine, and ondansetron.

20. The article of claim 1 , wherein the article is configured to deliver at least 1 μg of active pharmaceutical agent per square centimeter of a tissue of a subject, and/or wherein the article comprises greater than or equal to 1 mg of active pharmaceutical agent per square centimeter.

21. The article of claim 14 , wherein the article comprises at least a first portion having an average density greater than 1 g/cm 3 wherein a longitudinal axis perpendicular to a tissue-engaging surface of the article is configured to maintain an orientation of 20 degrees or less from vertical when acted on by 0.09*10{circumflex over ( )}−4 Nm or less of externally applied torque.

Assignees

• Massachusetts Inst Technology
• Brigham & Womens Hospital Inc

Inventors

• Traverso Carlo Giovanni
• Abramson Alex G
• Caffarel Salvador Ester
• Roxhed Niclas
• Khang Minsoo
• Bensel Taylor
• Langer Robert S

Classifications

• A61M2205/106

  reciprocating · CPC title

• A61K47/42

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61M2037/0007

  having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents · CPC title

• A61M37/00

  Other apparatus for introducing media into the body (for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30); Percutany, i.e. introducing medicines into the body by diffusion through the skin (salt baths A61H33/04) · CPC title