# US 2019/0167754 A1 · Process for the preparation of pharmaceutical compositions for the sustained release of somatostatin analogs

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- Number: US 2019/0167754 A1
- Document ID: US20190167754A1
- Status: Published application
- Kind: A1
- Application number: 16/232,207
- Filed: 2018-12-26
- Published: 2019-06-06
- Earliest claimed: 2010-01-13
- Assignees: Ipsen Pharma S.A.S.
- Applicants: Ipsen Pharma S.A.S.
- Inventors: Martin MONTES; Thomas Ciaran Loughman; Chantal Roume; Roland Cherif-Cheikh
- Web page: https://patentgrep.com/patent/US20190167754A1

## CPC

- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 38/31: Somatostatins
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61P 5/02: of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A61P 5/08: for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Process for the preparation of an injectable pharmaceutical composition for the sustained release of somatostatin analogues. Composition prepared according to such a process.

## Claims

### Claim 1

A process for preparing an injectable sustained release pharmaceutical composition, the process comprising the steps of:
lyophilizing a mixture comprising a somatostatin analog salt and an aqueous acid solution; and
hydrating the resulting lyophilizate;
wherein:
the lyophilization is performed only once; and
the final pH of the composition is from 5 to 7.

### Claim 2 (depends on 1)

The process of claim 1, wherein the somatostatin analog is lanreotide.

### Claim 3 (depends on 1)

The process of claim 1, wherein the acid is acetic acid.

### Claim 4 (depends on 1)

The process of claim 1, wherein the final pH of the composition is from 5.8 to 6.4.

### Claim 5 (depends on 1)

The process of claim 1, wherein the aqueous acid solution contains acetic acid at a concentration suitable for providing the requisite final pH.

### Claim 6 (depends on 1)

The process of claim 1, wherein the lyophilizate is hydrated with a solution containing acetic acid at a concentration suitable to provide a composition having an anhydrous acetate content of 9.1 to 10.5% by weight.

### Claim 7 (depends on 1)

The process of claim 1, wherein a 23 to 27 g/l lanreotide composition and a 13 to 17% by weight acetic acid composition are combined to form the mixture.

### Claim 8

(canceled)

### Claim 9 (depends on 7)

The process of claim 7, wherein the lyophilization occurs over a period of at least 40 hours.

### Claim 10 (depends on 7)

The process of claim 7, wherein the temperature of the mixture is:
reduced over a period of up to 30 minutes and then retained constant for 2 to 4 hours;
further reduced over a period of up to 15 minutes and then retained constant for 2.5 to 4.5 hours;
increased over a period of 15 to 25 hours and then retained constant for at least 40 hours; and
further increased over a period of 0.5 to 1.5 hours and then retained constant for at least 16 hours.

### Claim 11 (depends on 10)

The process of claim 10, wherein, after the temperature of the mixture is reduced, the atmospheric pressure is reduced to 15 to 25 μbar and remains constant as the temperature of the mixture increases.

### Claim 12 (depends on 1)

The process of claim 1, wherein the lyophilizate is hydrated by dissolving it in an amount of water that is less than 50% of the amount needed to completely dissolve the lanreotide salt.

### Claim 13 (depends on 1)

A sustained release pharmaceutical composition prepared according to the process of claim 1.

### Claim 14 (depends on 13)

The composition of claim 13, the composition being capable of releasing the lanreotide in vivo over a period of at least 15 days.

### Claim 15 (depends on 13)

The composition of claim 13, wherein the composition comprises from 15 to 35% by weight lanreotide base.

### Claim 16 (depends on 13)

The composition of claim 13, wherein the composition is suitable for use after storage for more than 12 months at a temperature of between 2 and 8° C.