# US 2019/0167706 A1 · Solid Pharmaceutical Composition Comprising Amorphous Sofosbuvir

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- Number: US 2019/0167706 A1
- Document ID: US20190167706A1
- Status: Published application
- Kind: A1
- Application number: 16/324,674
- Filed: 2017-08-09
- Published: 2019-06-06
- Earliest claimed: 2016-08-12
- Assignees: Sandoz Ltd.
- Applicants: Sandoz AG
- Inventors: Stefano Seminara; Agnieszka Tajchert; Franz Schwarz
- Web page: https://patentgrep.com/patent/US20190167706A1

## CPC

- A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
- A61K 9/143: {with inorganic compounds}
- A61K 9/145: {with organic compounds}
- A61K 9/146: {with organic macromolecular compounds}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 31/14: for RNA viruses
- A61K 9/1611: {Inorganic compounds}
- 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

It is provided a solid pharmaceutical composition comprising sofosbuvir, one or more pharmaceutically acceptable excipients and optionally at least one pharmaceutically acceptable matrix compound, wherein at least 99 weight-% of the sofosbuvir comprised in the solid pharmaceutically composition are present in amorphous form. Sofosbuvir amorphous form is stable in the solid pharmaceutical composition.

## Claims

### Claim 1

A solid pharmaceutical composition wherein the solid pharmaceutical composition comprises sofosbuvir according to formula (I)
and one or more pharmaceutically acceptable excipient(s), wherein at least 99 weight-% of the sofosbuvir comprised in the solid pharmaceutical composition are present in amorphous form, and at least 99 weight-% of the solid pharmaceutical composition consists of the sofosbuvir and the one or more pharmaceutically acceptable excipient(s).

### Claim 2

A solid pharmaceutical composition wherein the solid pharmaceutical composition comprises sofosbuvir according to formula (I)
at least one pharmaceutically acceptable matrix compound and one or more pharmaceutically acceptable excipient(s), wherein at least 99 weight-% of the sofosbuvir comprised in the solid pharmaceutical composition are present in amorphous form, and at least 99 weight-% of the solid pharmaceutical composition consists of the sofosbuvir, the at least one matrix compound and the one or more pharmaceutically acceptable excipient(s).

### Claim 3 (depends on 1)

The solid pharmaceutical composition claim 1, wherein the solid pharmaceutical composition is a solid dispersion.

### Claim 4 (depends on 1)

The solid pharmaceutical composition of claim 1, wherein the solid pharmaceutical composition comprises the sofosbuvir in an amount in the range of from 15 to 95 weight-%.

### Claim 5 (depends on 1)

The solid pharmaceutical composition of claim 1, wherein the solid pharmaceutical composition comprises the sofosbuvir in an amount in the range from 20 to 40 weight-%, based on the total weight of the solid pharmaceutical composition.

### Claim 6 (depends on 2)

The solid pharmaceutical composition of claim 2, wherein the at least one matrix compound is selected from the group consisting of hydrophilic polymers, silicon-based inorganic adsorbents and a combination of two or more thereof.

### Claim 7 (depends on 6)

The solid pharmaceutical composition of claim 6, wherein the silicon-based inorganic adsorbents include one or more of silica and silicates.

### Claim 8 (depends on 7)

The solid pharmaceutical composition of claim 7, wherein the hydrophilic polymers include one or more of polysaccharides, polyvinylpyrrolidones, polyethylene glycols, polyethylene glycol based copolymers, polyacrylic acids, salts of polyacrylic acids, polyvinyl alcohols, polyacrylamide copolymers, methacrylic acid copolymers, methacrylate copolymers, pectines, chitin derivatives, chitosan derivatives, polyphosphates, polyoxazolines.

### Claim 9 (depends on 8)

The solid pharmaceutical composition of claim 8, wherein the hydrophilic polymers include copovidone.

### Claim 10 (depends on 1)

The solid pharmaceutical composition of claim 1, wherein at least 1.5 weight-% of the solid pharmaceutical composition consists of the one or more pharmaceutically acceptable excipients based on the total weight of the solid pharmaceutical composition.

### Claim 11 (depends on 1)

The solid pharmaceutical composition of claim 1, obtainable or obtained by a process comprising
(i) preparing amorphous sofosbuvir;
(ii) mixing the amorphous sofosbuvir of (i) and one or more pharmaceutically acceptable excipient(s), wherein at least 99 weight-% of the mixture consists of the sofosbuvir and the one or more pharmaceutically acceptable excipient(s);
(iii) processing the mixture obtained from (ii) to the solid pharmaceutical composition.

### Claim 12 (depends on 10)

The solid pharmaceutical composition of claim 10, wherein the preparing of (i) is carried out by rapid drying a solution comprising sofosbuvir and one or more solvents.

### Claim 13 (depends on 2)

The solid pharmaceutical composition of claim 2, obtainable or obtained by a process comprising
(i) preparing a mixture comprising sofosbuvir, at least one pharmaceutically acceptable matrix compound and one or more pharmaceutically acceptable excipient(s), wherein at least 99 weight-% of the mixture consists of the sofosbuvir, the at least one matrix compound and the one or more pharmaceutically acceptable excipient(s);
(ii) processing the mixture obtained from (i) to the solid pharmaceutical composition.

### Claim 14 (depends on 13)

The solid pharmaceutical composition of claim 13, wherein (ii) comprise one or more of wet granulation, dry granulation, compression, melting extrusion of the mixture of (i).

### Claim 15 (depends on 2)

The solid pharmaceutical composition of claim 2, obtainable or obtained by a process comprising
(i′) preparing a mixture of sofosbuvir and the at least one pharmaceutically acceptable matrix compound and at least one solvent;
(ii′) subjecting the mixture of (i′) to drying, obtaining a dried mixture-1;
(iii′) mixing the mixture-1 of (ii′) with the one or more pharmaceutically acceptable excipient(s), obtaining a mixture-2;
(iv′) processing the mixture-2 of (iii′) to the solid pharmaceutical composition.

### Claim 16 (depends on 1)

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

### Claim 17 (depends on 1)

A process for preparing a solid pharmaceutical composition according to claim 1, the process comprising:
(i) preparing amorphous sofosbuvir,
(ii) mixing the amorphous sofosbuvir of (i) and one or more pharmaceutically acceptable excipient(s), wherein at least 99 weight-% of the mixture consists of the sofosbuvir and the one or more pharmaceutically acceptable excipient(s);
(iii) processing the mixture obtained from (ii) to the solid pharmaceutical composition.

### Claim 18 (depends on 17)

The process of claim 17 wherein the preparing of (i) is carried out by rapid drying a solution comprising sofosbuvir and one or more solvents.

### Claim 19

A process for preparing a solid pharmaceutical composition, the process comprising:
(i) preparing a mixture comprising sofosbuvir, at least one pharmaceutically acceptable matrix compound and one or more pharmaceutically acceptable excipient(s), wherein at least 99 weight-% of the mixture consists of the sofosbuvir, the at least one matrix compound and the one or more pharmaceutically acceptable excipient(s);
(ii) processing the mixture obtained from (i) to the solid pharmaceutical composition.

### Claim 20 (depends on 19)

The process of claim 19, wherein (ii) comprise one or more of wet granulation, dry granulation, compression, melting extrusion of the mixture of (i).

### Claim 21

A process for preparing a solid pharmaceutical composition, the process comprising:
(i′) preparing a mixture of sofosbuvir and the at least one pharmaceutically acceptable matrix compound and at least one solvent;
(ii′) subjecting the mixture of (i′) to drying the mixture of (i′), obtaining a dried mixture-1;
(iii′) mixing the mixture-1 of (ii′) with the one or more pharmaceutically acceptable excipient(s), obtaining a mixture-2;
(iv′) processing the mixture-2 of (iii′) to the solid pharmaceutical composition.