Pharmaceutical dosage form for immediate release of an indolinone derivative

Patent metadata

Field	Value
Publication number	US-10105323-B2
Application number	US-201715590487-A
Country	US
Kind code	B2
Filing date	May 9, 2017
Priority date	Jun 6, 2008
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

The present invention relates to a pharmaceutical dosage form delivering an immediate release profile containing the active substance 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone-monoethanesulphonate.

First claim

The invention claimed is:

1. A pharmaceutical dosage form which is a viscous lipid suspension formulation comprising:
10 to 50 wt. % of the active substance 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylenel]-6-methoxycarbonyl-2-indolinone-monoethanesulphonate,
10 to 70 wt. % of medium chain triglycerides;
10 to 30 wt. % of hard fat; and
0.25 to 2.5 wt. % of lecithin,
which delivers an immediate release profile in which not less than 70% (Q65%) of the active substance is dissolved in 60 minutes in vitro under the following in vitro dissolution conditions according to European Pharmacopeia 6.2: Apparatus 2 (paddle), dissolution medium with 0.1 M HCl (pH 1) and stirring speed of 50 to 150 rpm, at a temperature of 37° C.

2. The pharmaceutical dosage form according to claim 1 , wherein it is an orally deliverable dosage form.

3. The pharmaceutical dosage form according to claim 2 , wherein it is in the form of a capsule.

4. The pharmaceutical dosage form according to claim 3 in the form of a soft gelatine capsule comprising 50 mg of active substance free base equivalent selected from the group consisting of compositions A, B and C:

Formulation
Formulation
Formulation

A
B
C

mg per
mg per
mg per

Ingredients
capsule
capsule
capsule

Active
60.20
60.20
60.20

Substance*

Triglycerides,
40.95
53.70
54.00

Medium-chain

Hard fat
38.25
25.50
25.50

Lecithin
0.60
0.60
0.30

Gelatin
72.25
72.25
72.25

Glycerol 85%
32.24
32.24
32.24

Titanium
0.20
0.20
0.20

dioxide

Iron oxide A
0.32
0.32
0.32

Iron oxide B
0.32
0.32
0.32

Total Capsule Weight
245.33
245.33
245.33.

5. The pharmaceutical dosage form according to claim 3 in the form of a soft gelatine capsule comprising 75 mg of active substance free base equivalent selected from the group consisting of A, B and C:

Formulation
Formulation
Formulation

A
B
C

mg per
mg per
mg per

Ingredients
capsule
capsule
capsule

Active
90.3
90.3
90.3

Substance*

Triglycerides,
61.425
80.55
80.1

Medium-chain

Hard fat
57.375
38.25
38.25

Lecithin
0.9
0.9
1.35

Gelatin
107.11
107.11
107.11

Glycerol 85%
46.84
46.84
46.84

Titanium
0.35
0.35
0.35

dioxide

Iron oxide A
0.058
0.058
0.058

Iron oxide B
0.16
0.16
0.16

Total Capsule Weight
364.518
364.518
364.518.

6. The pharmaceutical dosage form according to claim 3 in the form of a soft gelatine capsule comprising 100 mg of active substance free base equivalent selected from the group consisting of compositions A, B and C:

Formulation
Formulation
Formulation

Assignees

• Boehringer Ingelheim Int

Inventors

• Messerschmid Roman
• Lach Peter
• Sokoliess Torsten
• Stopfer Peter
• Trommeshauser Dirk

Classifications

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/5078 Primary

  with drug-free core · CPC title

• A61K9/10

  Dispersions; Emulsions · CPC title

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07F9/572

  Five-membered rings · CPC title