# US 10,500,280 B2 · Orally dissolving melatonin formulation with acidifying agent that renders melatonin soluble in saliva

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- Number: US 10,500,280 B2
- Document ID: US10500280B2
- Status: Granted
- Kind: B2
- Application number: 16/009,372
- Filed: 2018-06-15
- Published: 2018-12-20
- Granted: 2019-12-10
- Earliest claimed: 2017-06-20
- Assignees: Physician's Seal, LLC
- Applicants: Physician's Seal, LLC
- Inventors: Syed M. Shah; Daniel Hassan; Fred Hassan; Patrick Corsino
- Web page: https://patentgrep.com/patent/US10500280B2

## CPC

- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 9/0056: {Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals}
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)}
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 25/20: Hypnotics; Sedatives
- 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 composition includes a pharmaceutical dosage form configured to dinsintegrate in saliva and maintain a pH of 4 or less within the saliva during the time the dosage form is dissolving therein. The dosage form includes a therapeutically effective amount of melatonin in a carrier matrix, a disintegrant, and a sufficient amount of acid to impart the pH to the saliva. The amount of disintegrant is sufficient to cause the dosage form to completely disintegrate in the saliva within ten minutes from contacting the saliva.

## Claims

### Claim 1

A composition comprising a pharmaceutical dosage form configured to disintegrate in oral saliva and maintain a pH of 4 or less within the saliva during the time the dosage form is dissolving therein, the dosage form including a therapeutically effective amount of melatonin in a carrier matrix, a disintegrant, and a sufficient amount of acid to impart the pH to the saliva, the amount of disintegrant being sufficient to cause the dosage form to completely disintegrate in the saliva, wherein the dosage form is at least one of a sublingual tablet and a buccal tablet within ten minutes from contacting the saliva.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the dosage form is at least 20% w/w of the acid.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the dosage form is a buccal tablet, that is at least 6% w/w disintegrant.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the dosage form is a sublingual tablet, that is at least 15% w/w disintegrant.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the therapeutically effective amount of melatonin is 0.2 mg to 20 mg.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the dosage form is a tablet and the carrier matrix includes microcrystalline cellulose in at least 45% w/w of the dosage form, the acid in at least 20% w/w of the dosage form, and the disintegrant in at least 6% w/w of the dosage form.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the acid is a carboxylic acid.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the acid is citric acid.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the amount of disintegrant is sufficient to cause the dosage form to completely disintegrate in the saliva within 2 minutes from contacting the saliva.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the amount of disintegrant is sufficient to cause the dosage form to completely disintegrate in the saliva within 1 minute from contacting the saliva.

### Claim 11

A method comprising administering a composition comprising a pharmaceutical dosage form to a subject in need thereof, the pharmaceutical dosage form dissolving in the subject's saliva while maintaining a pH of 4 or less within the saliva during the time the dosage form is dissolving, the dosage form including a therapeutically effective amount of melatonin in a carrier matrix, a disintegrant, and a sufficient amount of acid to impart the pH to the saliva, the amount of disintegrant being sufficient to cause the dosage form to completely disintegrate in the saliva within ten minutes from contacting the saliva, wherein the dosage form is at least one of a sublingual tablet and a buccal tablet.

### Claim 12 (depends on 11)

The method of claim 11, wherein the dosage form is at least 20% w/w of the acid.

### Claim 13 (depends on 11)

The method of claim 11, wherein the dosage form is a buccal tablet, that is at least 6% w/w disintegrant.

### Claim 14 (depends on 11)

The method of claim 11, wherein the dosage form is a sublingual tablet, that is at least 15% w/w disintegrant.

### Claim 15 (depends on 11)

The method of claim 11, wherein the therapeutically effective amount of melatonin is 0.2 mg to 20 mg.

### Claim 16 (depends on 11)

The method of claim 11, wherein the carrier matrix includes microcrystalline cellulose in at least 45% w/w of the dosage form, the acid in at least 20% w/w of the dosage form, and the disintegrant in at least 6% w/w of the dosage form.

### Claim 17 (depends on 11)

The method of claim 11, wherein administering occurs within 30 minutes of the time the subject desires to fall asleep.

### Claim 18 (depends on 11)

The method of claim 11, wherein administering occurs at night after the subject has awoken from sleep and desires to fall back asleep.

### Claim 19 (depends on 11)

The method of claim 11, wherein the acid is a carboxylic acid.

### Claim 20 (depends on 11)

The method of claim 11, wherein the acid is citric acid.

### Claim 21 (depends on 11)

The method of claim 11, wherein the amount of disintegrant is sufficient to cause the dosage form to completely disintegrate in the saliva within 2 minutes from contacting the saliva.

### Claim 22 (depends on 11)

The method of claim 11, wherein the amount of disintegrant is sufficient to cause the dosage form to completely disintegrate in the saliva within 1 minute from contacting the saliva.

### Claim 23

A composition comprising:
a pharmaceutical dosage form configured to disintegrate in saliva and maintain a pH of 4 or less within the saliva during the time the dosage form is dissolving therein, the dosage form including:
2% w/w to 20% w/w melatonin in a therapeutically effective amount;
a carrier matrix including 45% w/w to 68% w/w filler, 6% w/w to 20% w/w disintegrant, the amount of disintegrant being sufficient to cause the dosage form to completely disintegrate in the saliva within ten minutes from contacting the saliva; and
20% w/w to 30% w/w acid, the amount of acid being effective to impart the pH to the saliva, wherein the dosage form is at least one of a sublingual tablet and a buccal tablet.

### Claim 24 (depends on 23)

The composition of claim 23, wherein the disintegrant includes crospovidone, the filler includes microcrystalline cellulose, and the acid includes citric acid.

### Claim 25 (depends on 23)

The composition of claim 23, wherein the dosage form is a sublingual tablet and the disintegrant is present in at least 15% w/w of the dosage form.

### Claim 26 (depends on 23)

The composition of claim 23, wherein the therapeutically effective amount of melatonin is 0.2 mg to 20 mg.

### Claim 27 (depends on 23)

The composition of claim 23, wherein the acid is a carboxylic acid.

### Claim 28 (depends on 23)

The composition of claim 23, wherein the acid is citric acid.

### Claim 29 (depends on 23)

The composition of claim 23, wherein the amount of disintegrant is sufficient to cause the dosage form to completely disintegrate in the saliva within 2 minutes from contacting the saliva.

### Claim 30 (depends on 23)

The composition of claim 23, wherein the amount of disintegrant is sufficient to cause the dosage form to completely disintegrate in the saliva within 1 minute from contacting the saliva.