# US 12,005,041 B2 · Misoprostol dispersible tablet

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- Number: US 12,005,041 B2
- Document ID: US12005041B2
- Status: Granted
- Kind: B2
- Application number: 17/861,711
- Filed: 2022-07-11
- Published: 2022-11-03
- Granted: 2024-06-11
- Earliest claimed: 2014-07-11
- Assignees: Azanta Danmark A/S
- Applicants: Azanta Danmark A/S
- Inventors: Selvaraj Sekar; Elumalai Baskar; Arunachalam Malaiarasan; Venugopal Prabhakaran
- Web page: https://patentgrep.com/patent/US12005041B2

## CPC

- A61K 31/215: of carboxylic acids
- A61K 9/0034: {Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants}
- 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 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin}
- A61K 31/5575: having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 15/04: for inducing labour or abortion; Uterotonics
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2121/00: Preparations for use in therapy
- 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

The present invention relates to a solid pharmaceutical formulation comprising misoprostol or a pharmaceutically acceptable salt thereof. In particular, the invention relates to a dispersible tablet comprising misoprostol or a pharmaceutically acceptable salt thereof, providing alternative routes of administration. The tablet is particularly suited for cervical ripening, induction of labor, prevention and/or treatment of postpartum or post-abortion hemorrhage.

## Claims

### Claim 1

A pharmaceutical tablet comprising misoprostol, or a pharmaceutically acceptable salt thereof, as the sole active ingredient; wherein the tablet has a content of 0.5-50 μg misoprostol, or an equivalent amount of a pharmaceutically acceptable salt thereof; and wherein the tablet further comprises:
i) 5-20 wt % crospovidone,
ii) 5-20 wt % of a cross-linked polymer of carboxymethyl cellulose or a crosslinked sodium carboxymethyl cellulose,
iii) 5-20 wt % starch,
iv) 30-85 wt % microcrystalline cellulose, and
v) 0.1-2 wt % flow agent, subject to the proviso that the total of ingredients i) through v) and the misoprostol, or a pharmaceutically acceptable salt thereof, does not exceed 100 wt %, and wherein the tablet is suitable for sublingual or oral administration and is an immediate release tablet.

### Claim 2 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein the tablet is suitable for use in a treatment comprising cervical ripening or induction of labor upon administration to a subject.

### Claim 3 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein said tablet is suitable for administration to a pregnant woman.

### Claim 4 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein said pharmaceutical tablet comprises:
i. crospovidone at about 10 wt %,
ii. croscarmellose sodium at about 10 wt %, and
iii. starch at about 10 wt %.

### Claim 5 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein said pharmaceutical tablet comprises 70 wt % microcrystalline cellulose.

### Claim 6 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein said flow agent is 1 wt % colloidal silicon dioxide.

### Claim 7 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein said starch is maize starch.

### Claim 8 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein the tablet is free of any extended release agents.

### Claim 9 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein the tablet comprises a coating.

### Claim 10 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein the tablet has a disintegration time of less than 15 seconds as measured using Disintegration Apparatus A according to European Pharmacopoeia 8.0, wherein the apparatus comprises a basket without disc and the basket comprises 6 tubes, and wherein the apparatus is operated after placing one pharmaceutical tablet in each of the 6 tubes and using an aqueous medium as the immersion fluid, maintained at 37±2° C.

### Claim 11 (depends on 10)

The pharmaceutical tablet according to claim 10, wherein said tablet has a disintegration time of less than 10 seconds.

### Claim 12 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein the tablet disintegrates upon contact with 10 drops of water.

### Claim 13 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein the tablet disintegrates upon contact with 3 drops of water.

### Claim 14 (depends on 1)

The tablet according to claim 1, wherein said tablet allows dispersion in 100 ml water at 25° C. within 3 minutes upon stirring, thereby providing a dispersion, said dispersion passing through a sieve screen with a nominal mesh aperture of 710 μm, wherein the tablet cannot pass through the sieve screen before dispersion in water.

### Claim 15 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein said tablet allows dispersion in 100 ml water at 25° C. within 1 minute, upon stirring, thereby providing a dispersion, said dispersion passing through a sieve screen with a nominal mesh aperture of 710 μm, wherein the dosage formtablet cannot pass through the sieve screen before dispersion in water.

### Claim 16 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein the tablet, upon being placed on three drops of water on a glass plate which is subsequently tilted at a 90 degrees angle, slides.

### Claim 17 (depends on 16)

The pharmaceutical tablet according to claim 16, wherein the tablet, upon being placed on three drops of water on a glass plate which is subsequently tilted at a 90 degrees angle, slides without adhering to the glass plate.

### Claim 18

A pharmaceutical tablet comprising misoprostol, or a pharmaceutically acceptable salt thereof, as the sole active ingredient; wherein the tablet has a content of 0.5-50 μg misoprostol, or an equivalent amount of a pharmaceutically acceptable salt thereof; and wherein the tablet further comprises:
i) 8-12 wt % crospovidone,
ii) 8-12 wt % of a cross-linked polymer of carboxymethyl cellulose or a crosslinked sodium carboxymethyl cellulose,
iii) 5-12 wt % starch,
iv) 60-75 wt % microcrystalline cellulose, and
v) 0.1-2 wt % flow agent, subject to the proviso that the total of ingredients i) through v) and the misoprostol, or a pharmaceutically acceptable salt thereof, does not exceed 100 wt %, and wherein the tablet is suitable for sublingual or oral administration and is an immediate release tablet.

### Claim 19 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein said tablet allows dispersion in 100 ml water at 25° C. within 30 seconds, upon stirring, thereby providing a dispersion, said dispersion passing through a sieve screen with a nominal mesh aperture of 710 μm, wherein the tablet cannot pass through the sieve screen before dispersion in water.

### Claim 20 (depends on 1)

The pharmaceutical tablet according to claim 1, wherein the tablet has a content of 25-50 μg misoprostol, or an equivalent amount of a pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 18)

The pharmaceutical tablet according to claim 18, wherein the tablet has a content of 25-50 μg misoprostol, or an equivalent amount of a pharmaceutically acceptable salt thereof.