Microparticles comprising gnrh made by pgss

Patent metadata

Field	Value
Publication number	US-2016228494-A1
Application number	US-201415027754-A
Country	US
Kind code	A1
Filing date	Oct 7, 2014
Priority date	Oct 8, 2013
Publication date	Aug 11, 2016
Grant date	—

Abstract

A pharmaceutical formulation comprising a solid matrix of one or more biodegradable polymers, the solid matrix including a pharmaceutically active substance or a pharmaceutically acceptable salt thereof distributed homogeneously or substantially homogeneously within the matrix; wherein the pharmaceutically active substance is, for example, a gonadotropin releasing hormone (GnRH), a GnRH agonist or a GnRH antagonist.

First claim

1 . A pharmaceutical formulation comprising a solid matrix of one or more biodegradable polymers, the solid matrix including a pharmaceutically active substance or a pharmaceutically acceptable salt thereof distributed homogeneously or substantially homogeneously within the matrix; wherein the pharmaceutically active substance is gonadotropin releasing hormone (GnRH), a GnRH agonist or a GnRH antagonist.

2 . A pharmaceutical formulation according to claim 1 wherein the pharmaceutically active substance is degarelix.

3 . A pharmaceutical formulation according to claim 1 or 2 further comprising one or more excipients.

4 . A pharmaceutical formulation according to claim 3 wherein the excipient is distributed homogeneously or substantially homogeneously within the matrix.

5 . A pharmaceutical formulation according to claim 3 or 4 wherein the excipient is selected from a sugar (e.g. trehalose), a sugar alcohol (e.g. mannitol), an inorganic salt (e.g. sodium chloride), a synthetic polymer (e.g. polyethylene oxide, PEO).

6 . A pharmaceutical formulation according to any preceding claim wherein the (or each) synthetic biodegradable polymer is a polyhydroxy acid (PHA), such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), a copolymer of lactic and glycolic acid (PLGA), a copolymer of lactic and glycolic acid with poly(ethylene glycol), poly(e-caprolactone) (PCL) or poly(3-hydroxybutyrate) (PHB).

7 . A pharmaceutical formulation according to any preceding claim wherein the (or each) biodegradeable polymer is a copolymer of lactic and glycolic acid (PLGA).

8 . A pharmaceutical formulation according to any preceding claim wherein the matrix is a solid matrix of a biodegradeable polymer which is a copolymer of lactic and glycolic acid (PLGA).

9 . A pharmaceutical formulation according to claim 7 or claim 8 wherein the PLGA has a molar ratio of lactic acid:glycolic acid of from 90:10 to 10:90, for example from 60:40 to 90:10, for example from 50:50 to 75:25.

10 . A pharmaceutical formulation according to any preceding claim wherein the inherent viscosity of the biodegradeable polymer is from about 0.1 to about 0.5 dL/g, for example 0.1 to about 0.5 dL/g.

11 . A pharmaceutical formulation according to any of claims 2 to 10 wherein the amount of degarelix in the pharmaceutical formulation is 5 to 40% by weight of the solid matrix.

12 . A pharmaceutical formulation according to any preceding claim wherein the matrix has been washed after formation in water, a C 1 to C 8 alcohol or a solution of a C 1 to C 8 alcohol in water.

13 . A pharmaceutical formulation according to any preceding claim obtained by or obtainable by a process comprising the steps of:
(a) providing in a vessel the biodegradable polymer in solid form, the pharmaceutically active substance or salt thereof in solid form, and optionally the excipient; (b) adding a solvent to the solid polymer and pharmaceutically active substance in the vessel; (c) adding a fluid which is capable of existing in the supercritical state to the vessel; (d) increasing the temperature and pressure in the vessel to convert the fluid to the supercritical state, optionally mixing the polymer, pharmaceutically active substance and excipient (if present) prior to, during, and/or after conversion of the fluid to the supercritical state; (e) decreasing the temperature and/or pressure in the vessel to convert the fluid to a sub-critical state; and then increasing the temperature and/or pressure in the vessel to return the fluid to the supercritical state; (f) optionally, repeating step (e) one or more times; (g) recovering the solid matrix; (h) optionally, washing the solid matrix.

14 . A pharmaceutical formulation comprising a solid matrix of one or more biodegradable polymers; a pharmaceutically active substance or a pharmaceutically acceptable salt thereof; and optionally an excipient, wherein the pharmaceutically active substance is gonadotropin releasing hormone (GnRH), a GnRH agonist or a GnRH antagonist; the formulation being obtained by or obtainable by a process comprising the steps of:
(a) providing in a vessel the biodegradable polymer(s) in solid form, the pharmaceutically active substance or salt thereof in solid form, and optionally the excipient; (b) adding a solvent to the solid polymer and pharmaceutically active substance in the vessel; (c) adding a fluid which is capable of existing in the supercritical state to the vessel; (d) increasing the temperature and pressure in the vessel to convert the fluid to the supercritical state, optionally mixing the polymer, pharmaceutically active substance and excipient (if present) prior to, during, and/or after conversion of the fluid to the supercritical state; (e) decreasing the temperature and/or pressure in the vessel to convert the fluid to a sub-critical state; and then increasing the temperature and/or pressure in the vessel to return the fluid to the supercritical state; (f) optionally, repeating step (e) one or more times; (g) recovering the solid matrix; (h) optionally, washing the solid matrix.

15 . A pharmaceutical formulation according to claim 13 or claim 14 obtained by or obtainable by a process wherein the fluid is carbon dioxide.

16 . A pharmaceutical formulation according to claim 13 , 14 or claim 15 obtained by or obtainable by a process wherein the solvent added in step (b) is an aprotic organic solvent such as dimetholsufoxide (DMSO) or acetone, or an alcohol.

17 . A pharmaceutical formulation according to any of claims 13 to 16 obtained by or obtainable by a process wherein the solid matrix is washed in water, a C 1 to C 8 alcohol or a solution of a C 1 to C 8 alcohol in water.

18 . A pharmaceutical formulation comprising a solid matrix of one or more biodegradable polymers having inherent viscosity from 0.1 to 0.5 dL/g; the solid matrix including a pharmaceutically active substance or a pharmaceutically acceptable salt thereof and optionally an excipient, wherein the pharmaceutically active substance is gonadotropin releasing hormone (GnRH), a GnRH agonist (e.g. triptorelin) or a GnRH antagonist.

19 . A pharmaceutical formulation according to any preceding claim wherein the solid matrix is in the form of microparticles.

20 . A pharmaceutical formulation according to claim 19 wherein the microparticles have mean particle size of from about 25 to about 65 μm expressed as the volume mean diameter (VMD).

21 . A pharmaceutical formulation comprising a solid matrix of one or more biodegradable polymers, the solid matrix including a pharmaceutically active substance or a pharmaceutically acceptable salt thereof distributed homogeneously or substantially homogeneously within the matrix; wherein the pharmaceutically active substance is gonadotropin releasing hormone (GnRH), a GnRH agonist (e.g. triptorelin), a GnRH antagonist (e.g. degarelix, e.g. degarelix acetate), a growth hormone (such as bovine growth hormone, human growth hormone, hGH, recombinant hGH), growth hormone releasing factor, somatostatin, vasopressin, a vasopressin analog (e.g. desmopressin, desmopressin acetate), glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), prolactin, octreotide (e.g. octreotide acetate), oxytocin or analog thereof (e.g. carbetocin), human menopausal gonadotropin (HMG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), or anti-IL-6 agent (IL-6 inhibitor).

22 . A pharmaceut

Assignees

• Ferring Bv

Inventors

• Schwach Gregoire Charles Joseph
• Schiefelbein Lars
• Naylor Andrew
• Whitaker Mark Andrew
• Arrowsmith Nicholas John

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P13/08

  of the prostate · CPC title

• A61K38/22

  Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35) · CPC title

• A61K47/30

  Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates · CPC title