Novel terpolymers and their use in pharmaceutical dosage forms

Patent metadata

Field	Value
Publication number	US-2021069112-A1
Application number	US-201816772273-A
Country	US
Kind code	A1
Filing date	Dec 7, 2018
Priority date	Dec 20, 2017
Publication date	Mar 11, 2021
Grant date	—

Abstract

Terpolymer, wherein 20 to 35% by weight of the structural units are derived from acrylic acid, 45 to 60% by weight of the structural units from a hydrophobic methacrylate selected from a group consisting of isopropyl methacrylate, tert-butyl methacrylate and cyclohexyl methacrylate and 15 to 40% by weight of the structural units from a third olefinic monomer selected from the group consisting of N-vinyl lactam, hydroxy ethyl methacrylate and phenoxyethyl acrylate with the proviso that the total amount of structural units derived from the three monomer groups adds up to 100% by weight, and the use of the terpolymers as crystallization inhibitors in pharmaceutical dosage forms for inhibiting the recrystallization in an aqueous environment of a human or animal body of an active ingredient.

First claim

1 . A terpolymer, wherein 20 to 35% by weight of the structural units are derived from acrylic acid, 45 to 60% by weight of the structural units from a hydrophobic methacrylate selected from a group consisting of isopropyl methacrylate, tert-butyl methacrylate and cyclohexyl methacrylate and 15 to 40% by weight of the structural units from a third olefinic monomer selected from the group consisting of N-vinyl lactam, hydroxy ethyl methacrylate and phenoxyethyl acrylate with the proviso that the total amount of structural units derived from the three monomer groups adds up to 100% by weight.

2 . The terpolymer according to claim 1 , wherein a solubility in phosphate buffer of a pH of 6.8 under standard conditions is such that a content of insoluble substances remaining on a membrane filter having an average pore size of 8 μm when a 0.3% by weight aqueous preparation of the terpolymer is filtered with the filter, is not higher than 25% by weight of the amount of terpolymer in the aqueous preparation.

3 . The terpolymer according to claim 1 , wherein the hydrophobic methacrylate is tert-butyl methacrylate.

4 . The terpolymer according to claim 1 , wherein the N-vinyl lactam is N-vinyl pyrrolidone.

5 . The terpolymer according to claim 1 , wherein the N-vinyl lactam is N-vinyl caprolactam.

6 . The terpolymer according to claim 1 , having a calculated glass transition temperature in the range of 80 to 150° C.

7 . The terpolymer according to claim 1 , having a calculated glass transition temperature in the range of 100 to 150° C.

8 . The terpolymer according to claim 1 , wherein an amount of tert-butyl methacrylate derived structural units lies in the range of 45 to 55% by weight.

9 . The terpolymer according to claim 1 , wherein the amount of acrylic acid derived structural units lies in the range of 20 to 30% by weight.

10 . The terpolymer according to claim 1 , wherein the amount of structural units derived from the third olefinic monomer lies in the range of 20 to 35% by weight.

11 . The terpolymer according to claim 1 , with having a weight average molecular weight in the range of 7,000 to 100,000 g/mol.

12 . The terpolymer according to claim 1 , wherein the terpolymer is partly neutralized to provide a pH in the range of 5 to 9 upon dissolution in water.

13 . A process for manufacturing a terpolymer according to claim 1 comprising a radical polymerization of the monomers in the presence of a free radical initiator.

14 . The process according to claim 13 , wherein the polymerization is a solution polymerization.

15 . The process according to claim 14 , wherein the solution polymerization is carried out in an organic solvent.

16 . The process according to claim 15 wherein the organic solvent is isopropanol.

17 . The process according to claim 13 , in which wherein the radical initiator is a peroxide.

18 . Pharmaceutical A pharmaceutical dosage form, comprising a terpolymer according to claim 1 and an active pharmaceutical ingredient with a solubility in water at standard conditions of less than 0.1% by weight, wherein the active ingredient is present in an amorphous form.

19 . A terpolymer according to claim 1 for use as a recrystallization inhibitor in a pharmaceutical dosage form for inhibiting recrystallization in an aqueous environment of a human or animal body of an active ingredient with a solubility in water at standard conditions of less than 0.1% by weight, wherein the active ingredient is present in such pharmaceutical dosage forms in an amorphous form.

20 . A method of inhibiting recrystallization of an active ingredient in an aqueous environment of a human or animal comprising administering a dosage form comprising the active ingredient and a terpolymer of claim 1 , wherein the active ingredient has a solubility in water at standard conditions of less than 0.1% by weight and is present in the pharmaceutical dosage form in an amorphous form.

Assignees

• Basf Se

Inventors

• Brandl Ferdinand Paul
• Smit Theo
• Guth Felicitas
• Kolter Karl
• Angel Maximilian
• Schmidt Frank

Classifications

• A61K47/32 Primary

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61K9/1635 Primary

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• C08F226/10

  N-Vinyl-pyrrolidone · CPC title

• C08F220/1806

  C6-(meth)acrylate, e.g. (cyclo)hexyl (meth)acrylate or phenyl (meth)acrylate · CPC title

• C08F220/1803

  C3-(meth)acrylate, e.g. (iso)propyl (meth)acrylate · CPC title