# US 2018/0021272 A1 · Formulations for oral administration of active agents

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- Number: US 2018/0021272 A1
- Document ID: US20180021272A1
- Status: Published application
- Kind: A1
- Application number: 15/549,436
- Filed: 2016-02-09
- Published: 2018-01-25
- Earliest claimed: 2015-02-09
- Assignees: Entera Bio Ltd.
- Applicants: Entera Bio Ltd.
- Inventors: Gregory BURSHTEIN; Ariel ROTHNER; Philip M. SCHWARTZ; Hillel GALITZER
- Web page: https://patentgrep.com/patent/US20180021272A1

## CPC

- A61K 38/29: Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2086: {Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat (active cores with a complete drug-free outer coat A61K9/28)}
- A61K 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)}
- A61K 9/2886: {having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer (of the type active core-drug layer-inactive layer A61K9/209)}
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60)
- A61K 31/20: having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K 38/22: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35)
- A61K 38/55: Protease inhibitors
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61P 5/18: of the parathyroid hormones
- A61P 19/10: for osteoporosis
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A pharmaceutical composition for oral administration is disclosed herein, comprising a therapeutically active agent, SNAC and at least one antacid compound. Further disclosed herein is a pharmaceutical composition unit dosage form for oral administration of a therapeutically active agent is provided herein, the unit dosage form comprising: a core comprising the therapeutically active agent and SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate); and an external layer comprising at least one protective agent selected from the group consisting of an antacid compound and a protease inhibitor. Methods and uses utilizing the aforementioned pharmaceutical compositions, as well as methods and uses utilizing co-administration, by oral administration, of at least one antacid composition, and a composition comprising the therapeutically active agent and SNAC, are further disclosed herein, for use in treating a condition treatable by oral administration of the therapeutically active agent.

## Claims

### Claim 1

A pharmaceutical composition for oral administration of a therapeutic active agent, the composition comprising a therapeutically active agent, SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate), and at least one antacid compound.

### Claim 2 (depends on 1)

The composition of claim 1, further comprising at least one protease inhibitor.

### Claim at position 3

3-4. (canceled)

### Claim 5 (depends on 1)

The composition of claim 1, wherein said at least one antacid compound is selected from the group consisting of calcium carbonate, calcium gluconate, calcium citrate, sodium carbonate, sodium bicarbonate, sodium gluconate, sodium citrate, sodium hydroxide, potassium carbonate, potassium bicarbonate, potassium gluconate, potassium citrate, potassium hydroxide, magnesium carbonate, magnesium gluconate, magnesium citrate, magnesium hydroxide, magnesium oxide, aluminum carbonate, aluminum gluconate, aluminum citrate, and aluminum hydroxide.

### Claim 6 (depends on 1)

The composition of claim 1, wherein at least 90 weight percents of the composition consists of ingredients selected from the group consisting of said therapeutically active agent, SNAC, and said at least one antacid compound.

### Claim 7 (depends on 1)

The composition of claim 1, wherein said therapeutically active agent has a molecular weight in a range of 0.5 kDa to 100 kDa.

### Claim 8 (depends on 1)

The composition of claim 1, wherein said therapeutically active agent is a polypeptide.

### Claim 9 (depends on 8)

The composition of claim 8, wherein said polypeptide is selected from the group consisting of a parathyroid hormone, insulin, a glucagon, an interferon, a growth hormone, an erythropoietin, a calcitonin, an omentin, a motilin, a leptin, a peptide YY, a GLP-1, a GLP-2, a granulocyte colony stimulating factor (G-CSF), an antibody, an interleukin, an erythropoietin, a vasopressin, a vasoactive intestinal peptide, a pituitary adenylate cyclase-activating peptide (PACAP), a blood clotting factor, an endomorphin, a TNF inhibitor, disitertide, octreotide, davunetide, icatibant, glucocerebrosidase, a gonadotropin releasing hormone, acyline, and a GLP-1 agonist.

### Claim at position 9

10-13. (canceled)

### Claim 14 (depends on 1)

The composition of claim 1, being formulated as a unit dosage form.

### Claim 15 (depends on 14)

The composition of claim 14, wherein said unit dosage form comprises at least 50 mg of SNAC.

### Claim at position 12

16-20. (canceled)

### Claim 21 (depends on 1)

A method of treating a condition treatable by oral administration of a therapeutically active agent in a subject in need thereof, the method comprising orally administering to the subject the composition of claim 1 to a subject in need thereof.

### Claim 22

A method of treating a condition treatable by oral administration of a therapeutically active agent in a subject in need thereof, the method comprising co-administering to the subject, by oral administration, an antacid composition comprising at least one antacid compound and/or at least one gastric acid secretion inhibitor, and a composition comprising said therapeutically active agent and SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate).

### Claim at position 15

23-24. (canceled)

### Claim 25 (depends on 22)

The method of claim 22, wherein said co-administering comprises administering said antacid composition prior to or concomitantly with said composition comprising said therapeutically active agent and SNAC.

### Claim 26 (depends on 22)

The method of claim 22, wherein said therapeutically active agent has a molecular weight in a range of 0.5 kDa to 100 kDa.

### Claim 27 (depends on 22)

The method of claim 22, wherein said therapeutically active agent is a polypeptide.

### Claim 28

A pharmaceutical composition unit dosage form for oral administration of a therapeutically active agent, the unit dosage form comprising:
a core comprising the therapeutically active agent and SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate); and
an external layer comprising at least one protective agent selected from the group consisting of an antacid compound and a protease inhibitor.

### Claim 29

(canceled)

### Claim 30 (depends on 28)

The unit dosage form of claim 28, wherein said external layer is devoid of SNAC.

### Claim 31 (depends on 28)

The unit dosage form of claim 28, wherein said external layer comprises at least one protease inhibitor.

### Claim at position 23

32-33. (canceled)

### Claim 34 (depends on 28)

The unit dosage form of claim 28, being coated with an enteric coating.

### Claim 35 (depends on 28)

The unit dosage form of claim 28, wherein said external layer and/or core comprises at least one antacid compound.

### Claim 36

(canceled)

### Claim 37 (depends on 35)

The unit dosage form of claim 35, wherein said at least one antacid compound is selected from the group consisting of calcium carbonate, calcium citrate, calcium gluconate, sodium carbonate, sodium bicarbonate, sodium gluconate, sodium citrate, sodium hydroxide, potassium carbonate, potassium bicarbonate, potassium gluconate, potassium citrate, potassium hydroxide, magnesium carbonate, magnesium gluconate, magnesium citrate, magnesium hydroxide, magnesium oxide, aluminum carbonate, aluminum gluconate, aluminum citrate, and aluminum hydroxide.

### Claim 38 (depends on 28)

The unit dosage form of claim 28, being soluble in gastric fluid.

### Claim 39 (depends on 28)

The unit dosage form of claim 28, being in a form of a tablet comprising said core and said external layer.

### Claim 40 (depends on 28)

The unit dosage form of claim 28, comprising at least 50 mg of SNAC.

### Claim 41 (depends on 28)

The unit dosage form of claim 28, wherein said therapeutically active agent has a molecular weight in a range of 0.5 kDa to 100 kDa.

### Claim 42 (depends on 28)

The unit dosage form of claim 28, wherein said therapeutically active agent is a polypeptide.

### Claim 43 (depends on 42)

The unit dosage form of claim 42, wherein said polypeptide is selected from the group consisting of a parathyroid hormone, insulin, a glucagon, an interferon, a growth hormone, an erythropoietin, a calcitonin, an omentin, a motilin, a leptin, a peptide YY, a GLP-1, a GLP-2, a granulocyte colony stimulating factor (G-CSF), an antibody, an interleukin, an erythropoietin, a vasopressin, a vasoactive intestinal peptide, a pituitary adenylate cyclase-activating peptide (PACAP), a blood clotting factor, an endomorphin, a TNF inhibitor, disitertide, octreotide, davunetide, icatibant, glucocerebrosidase, a gonadotropin releasing hormone, acyline, and a GLP-1 agonist.

### Claim 44

(canceled)

### Claim 45 (depends on 28)

The unit dosage form of claim 28, wherein said core and/or said external layer further comprises a pharmaceutically acceptable carrier.

### Claim at position 36

46-48. (canceled)

### Claim 49 (depends on 28)

A method of treating a condition treatable by oral administration of a therapeutically active agent in a subject in need thereof, the method comprising orally administering to the subject the unit dosage form of claim 28 to a subject in need thereof.