Manufacturing of semi-plastic pharmaceutical dosage units

Patent metadata

Field	Value
Publication number	US-10973759-B2
Application number	US-201916515762-A
Country	US
Kind code	B2
Filing date	Jul 18, 2019
Priority date	Nov 20, 2012
Publication date	Apr 13, 2021
Grant date	Apr 13, 2021

Abstract

A process for the manufacture of semi-plastic pharmaceutical unit doses using a rotary moulding machine and semi-plastic pharmaceutical dosage units obtained by this process.

First claim

What is claimed is:

1. A process for manufacturing of soft chewable veterinary pharmaceutical product for oral administration, wherein the soft chewable veterinary pharmaceutical product is formed with a rotary moulding machine, comprising the steps of:
a) mixing at least one active pharmaceutical ingredient with one or more components wherein the components are dry components and liquid components to prepare a premix,
b) heating a polyethylene glycol forming agent until melting,
c) mixing the premix and the polyethylene glycol forming agent together to form a dough,
d) feeding the dough into a container connected with a rotary moulding machine; and
e) forming a soft chewable veterinary pharmaceutical product for oral administration in a rotary moulding machine,
wherein the liquid component comprises one or more oils and the polyethylene glycol forming agent is solid at room temperature and has a melting point between 45° C. and 100° C.;
wherein the temperature of the dough in step d) is between 35° C. and 45° C.; and
wherein the rotary moulding machine does not have a knockoff mechanism or a punch mechanism.

2. The process according to claim 1 wherein the rotary moulding machine comprises forming moulds with concave edges.

3. The process according to claim 1 , wherein the active pharmaceutical ingredient is an isoxazoline compound of Formula (I)

wherein
R 1 =halogen, CF 3 , OCF 3 , CN,
n=integer from 0 to 3,
R 2 =C 1 -C 3 -haloalkyl,
T=5- or 6-membered ring, which is optionally substituted by one or more radicals Y,
Y=methyl, halomethyl, halogen, CN, NO 2 , NH 2 —C═S, or two adjacent radicals Y form together a chain;
Q=X—NR 3 R 4 or a 5-membered N-heteroaryl ring, which is optionally substituted by one or more radicals;
X=CH 2 , CH(CH 3 ), CH(CN), CO, CS,
R 3 =hydrogen, methyl, haloethyl, halopropyl, halobutyl, methoxymethyl, methoxyethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, N-phenyl-N-methyl-amino, haloethylaminocarbonylmethyl, haloethylaminocarbonylethyl, tetrahydrofuryl, methylaminocarbonylmethyl, (N,N-dimethylamino)-carbonylmethyl, propylaminocarbonylmethyl, cyclopropylaminocarbonylmethyl, propenylaminocarbonylmethyl, haloethylaminocarbonylcyclopropyl,

wherein Z A =hydrogen, halogen, cyano, halomethyl (CF 3 );
R 4 =hydrogen, ethyl, methoxymethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, methylcarbonyl, ethylcarbonyl, propylcarbonyl, cyclopropylcarbonyl, methoxycarbonyl, methoxymethylcarbonyl, aminocarbonyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, haloethylaminocarbonylmethyl, cyanomethylaminocarbonylmethyl, or haloethylaminocarbonylethyl;
Or R 3 and R 4 together form a substituent selected from the group consisting of:

or a salt or solvate thereof.

4. The process according to claim 3 wherein the active pharmaceutical ingredient is 4-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl-N-[(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzamide.

5. The process of claim 3 , wherein n is 1, 2 or 3.

6. The process of claim 3 , wherein R 2 is CF 3 or CF 2 Cl.

7. The process of claim 3 , wherein two adjacent radicals Y form together a three or four membered chain.

8. The process according to claim 1 wherein the active pharmaceutical ingredient is 4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide.

9. The process according to claim 1 wherein the liquid component comprises one or more oils and one or more non-aqueous solvents and a humectant.

10. The process according to claim 1 wherein the dry and liquid components are mixed to form a mouldable dough that is transported to a forming roll of the rotary moulding machine by a screw conveyor.

11. The process according to claim 1 wherein the soft chew is sucked out of a forming mould with a rough conveyor belt or a conveyor belt with vacuum suction.

12. The process according to claim 4 wherein the active pharmaceutical ingredient further comprises a milbemycin.

13. The process according to claim 12 wherein the milbemycin is milbemycin oxime.

Assignees

• Intervet Inc

Inventors

• Kluger Dominique
• Hauler Albin
• Schmidt Carsten
• Schroeckenfuchs David
• Waldron Niki

Classifications

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61P33/00

  Antiparasitic agents · CPC title

• A61K31/42

  Oxazoles · CPC title

• A61K9/2095

  Tabletting processes · CPC title

• A61K9/0056 Primary

  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 · CPC title