# US 11,026,892 B2 · Minimizing agglomeration of drug particle coating material during storage to stabilize disintegration times of pharmaceutical products

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- Number: US 11,026,892 B2
- Document ID: US11026892B2
- Status: Granted
- Kind: B2
- Application number: 17/008,318
- Filed: 2020-08-31
- Published: 2020-12-17
- Granted: 2021-06-08
- Earliest claimed: 2019-02-22
- Assignees: Catalent U.K. Swindon Zydis Limited
- Applicants: Catalent U.K. Swindon Zydis Limited
- Inventors: Rosaleen McLaughlin; Simon Andrew Martyn Howes; Craig Wheadon; Jonathon Whitehouse
- Web page: https://patentgrep.com/patent/US11026892B2

## CPC

- A61K 9/167: {with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface (with further drug-free outer coating A61K9/5073)}
- A61K 9/5063: {Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/5015)}
- 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 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules}
- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 9/1658: {Proteins, e.g. albumin, gelatin}
- A61K 9/2095: {Tabletting processes}
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- 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)

## Abstract

Provided are pharmaceutical compositions and methods for preparing pharmaceutical compositions using solventless mixing methods. Excess coating material that is not bound to a coated API particle may be removed by a sieving process. Coating and dosing ratios can also be optimized to minimize the amount of excess unbound coating material. Specifically, a coating ratio and/or a dosing ratio can be used to minimize the residual amount of excess unbound coating material to minimize agglomeration of coating material during storage. In some embodiments, a pharmaceutical composition is provided, the pharmaceutical composition comprising: 65-85% w/w API particles; 15-30% w/w coating material coating the API particles; and 3-15% w/w matrix surrounding the coated API particles, wherein the pharmaceutical composition comprises a disintegration time rate of less than 10 seconds for at least six months under storage conditions of at least 25° C. and at least 60% relative humidity.

## Claims

### Claim 1

A method of preparing a pharmaceutical composition comprising:
mixing active pharmaceutical ingredient (“API”) particles with a coating material comprising one or more deformable components;
exposing the mixture of API particles and coating material to mechanical and thermal energy to deform the one or more deformable components and form coated API particles;
mixing the coated API particles with silica;
exposing the mixture of coated API particles and silica to mechanical and thermal energy to at least one of adhere, partially embed, or embed the silica on the coated API particles, wherein the coated API particles comprise 0.5-5% w/w silica;
sieving the coated API particles comprising silica to remove excess coating material not bound to the coated API particles comprising silica;
mixing the coated API particles comprising silica into a matrix solution or suspension to form a pharmaceutical suspension;
dosing the pharmaceutical suspension into a mold;
freezing the pharmaceutical suspension in the mold; and
freeze drying the frozen pharmaceutical suspension to form the pharmaceutical composition.

### Claim 2 (depends on 1)

The method of claim 1, wherein a ratio used to combine the coated API particles comprising silica with the matrix solution or suspension comprises 5-60% w/w coated API particles comprising silica and 40-96% w/w matrix solution or suspension.

### Claim 3 (depends on 1)

The method of claim 1, further comprising sieving uncoated API particles.

### Claim 4 (depends on 1)

The method of claim 1, wherein sieving the coated API particles comprising silica comprises passing the coated API particles comprising silica through a device comprising two or more sieves.

### Claim 5 (depends on 1)

The method of claim 1, wherein sieving the coated API particles comprising silica comprises sieving the coated API particles comprising silica to an average particle size of 75-250 μm.

### Claim 6 (depends on 1)

The method of claim 1, wherein the API particles comprise one or more of anti-inflammatories, analgesics, anti-psychotics, anti-emetics, laxatives, anti-diarrheals, anti-histamines, or anti-depressants.

### Claim 7 (depends on 6)

The method of claim 6, wherein the API particles comprise Ibuprofen.

### Claim 8 (depends on 1)

The method of claim 1, wherein the one or more deformable components of the coating material comprises a wax.

### Claim 9 (depends on 8)

The method of claim 8, wherein the wax comprises one or more of carnauba wax, candelilla wax, or synthetic wax.

### Claim 10 (depends on 1)

The method of claim 1, wherein the matrix solution or suspension comprises a matrix former and a structure former.

### Claim 11 (depends on 10)

The method of claim 10, wherein the matrix former comprises one or more of a water soluble material, a water dispersible material, a polypeptide, a polysaccharide, polyvinyl alcohol, polyvinylpyrrolidone, and acacia.

### Claim 12 (depends on 11)

The method of claim 11, wherein the matrix former comprises a polypeptide.

### Claim 13 (depends on 12)

The method of claim 12, wherein the polypeptide comprises gelatin.

### Claim 14 (depends on 10)

The method of claim 10, wherein the structure former comprises one or more of mannitol, dextrose, lactose, galactose, and cyclodextrin.

### Claim 15 (depends on 14)

The method of claim 14, wherein the structure former comprises mannitol.