# US 9,750,710 B2 · Crystalline polymorphic forms of monosodium N-[-8-(2-hydroxybenzoyl)amino]caprylate

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- Number: US 9,750,710 B2
- Document ID: US9750710B2
- Status: Granted
- Kind: B2
- Application number: 15/049,313
- Filed: 2016-02-22
- Published: 2016-06-30
- Granted: 2017-09-05
- Earliest claimed: 2004-05-06
- Assignees: Emisphere Technologies, Inc.
- Applicants: Emisphere Technologies, Inc.
- Inventors: Halina Levchik; Shingai Majuru; Brahma Singh; Jamila Harris
- Web page: https://patentgrep.com/patent/US9750710B2

## CPC

- A61K 31/197: the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205)
- A61J 3/02: into the form of powders (pulverising in general B02C)
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2095: {Tabletting processes}
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/00: Drugs for disorders of the cardiovascular system
- C07C 235/60: having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- 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)
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention relates to crystalline polymorphic forms of monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate (“SNAC”), including two hydrates, a methanol solvate, and an ethanol solvate, of SNAC. More specifically, the present invention provide six polymorphic forms of SNAC (hereafter referred to as Forms I-VI). The present invention also provides an amorphous form of SNAC.

## Claims

### Claim 1

A pharmaceutical composition comprising a milled mixture of (a) crystalline anhydrous monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate exhibiting an X-ray powder diffraction pattern having a peak at 2.98±0.2° 2Θ and (b) at least one active agent, wherein the active agent is a peptide.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the crystalline anhydrous monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate further exhibits X-ray powder diffraction pattern peaks at 14.53, 15.72, and 26.36±0.2° 2Θ.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the milled mixture further comprises a pharmaceutically acceptable additive.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mixture comprises at least 50% by weight of the crystalline monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate, based on the total weight of monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate in the pharmaceutical composition.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mixture comprises at least 90% by weight of the crystalline monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate, based on the total weight of monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate in the pharmaceutical composition.

### Claim 6 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a tablet.

### Claim 7 (depends on 6)

The pharmaceutical composition of claim 6, wherein the tablet is prepared by direct compression.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein the X-ray powder diffraction pattern of the composition further exhibits peaks at 6.69, 13.58 and 16.80±0.2° 2Θ.

### Claim 9

A pharmaceutical composition comprising a milled mixture of (a) crystalline anhydrous monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate exhibiting a melting point onset at about 198° C. according to differential scanning calorimetry and (b) at least one active agent, wherein the active agent is a peptide.

### Claim 10 (depends on 9)

The pharmaceutical composition of claim 9, wherein the milled mixture further comprises a pharmaceutically acceptable additive.

### Claim 11 (depends on 9)

The pharmaceutical composition of claim 9, wherein the mixture comprises at least 50% by weight of the crystalline monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate, based on the total weight of monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate in the pharmaceutical composition.

### Claim 12 (depends on 9)

The pharmaceutical composition of claim 9, wherein the mixture comprises at least 90% by weight of the crystalline monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate, based on the total weight of monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate in the pharmaceutical composition.

### Claim 13 (depends on 9)

The pharmaceutical composition of claim 9, wherein the pharmaceutical composition is a tablet.

### Claim 14 (depends on 13)

The pharmaceutical composition of claim 13, wherein the tablet is prepared by direct compression.

### Claim 15 (depends on 9)

The pharmaceutical composition of claim 9, wherein the X-ray powder diffraction pattern of the composition exhibits peaks at 2.98, 6.69, 13.58 and 16.80±0.2° 2Θ.

### Claim 16

A process for preparing a pharmaceutical composition comprising wet granulating monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate exhibiting an X-ray powder diffraction pattern having a peak at 2.98±0.2° 2Θ with or without one or more active agents and/or pharmaceutically acceptable additives.

### Claim 17

A process for preparing a pharmaceutical composition comprising wet granulating monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate exhibiting a melting point onset at about 198° C. according to differential scanning calorimetry with or without one or more active agents and/or pharmaceutically acceptable additives.

### Claim 18 (depends on 16)

The process of claim 16, wherein the monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate in the wet granulated composition exhibits an X-ray powder diffraction pattern having peaks at 6.69, 13.58 and 16.80±0.2° 2Θ.

### Claim 19 (depends on 17)

The process of claim 17, wherein the monosodium N-[8-(2-hydroxybenzoyl)amino]caprylate in the wet granulated composition exhibits an X-ray powder diffraction pattern having peaks at 6.69, 13.58 and 16.80±0.2° 2Θ.

### Claim 20 (depends on 16)

The process of claim 16, wherein the wet granulation step is performed with an active agent, wherein the active agent is a peptide.

### Claim 21 (depends on 17)

The process of claim 17, wherein the wet granulation step is performed with an active agent, wherein the active agent is a peptide.

### Claim 22 (depends on 20)

A pharmaceutical composition prepared by a process according to claim 20.

### Claim 23 (depends on 21)

A pharmaceutical composition prepared by a process according to claim 21.