Oral suspension of pharmaceutical substance

• US 6,184,220 B1
• Filed: 03/25/1999
• Issued: 02/06/2001
• Est. Priority Date: 03/27/1998
• Status: Expired due to Term

• Current Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Pharmaceuticals Incorporated (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Schmelmer, Veit, Türck, Dietrich
• Primary Examiner(s): Harrison, Robert H.
• Application Number:
  US09/276,208
• Time in Patent Office: 684 Days
• Field of Search: 514/226.5, 514/937, 514/970, 514/974, 514/225.2, 514/225.8, 424/489, 424/494
• US Class Current: 514/226.5
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006

Abstract

The present invention relates to orally administered suspensions of pharmaceutical active substances of the NSAID type, particularly the antirheumatic agent Meloxicam, which are stabilized by the addition of small amounts of highly dispersed silicon dioxide using high shear forces and adding small amounts of hydrophilic polymers to form a three-dimensional siloid structure, and a process for the preparation thereof.

Claims

1. A pharmaceutical composition of matter which is an orally administered suspension comprising

particles of a non-steroidal anti-inflammtory active substance selected from the acid enolcarboxamides (oxicams), and pharmaceutically acceptable salts thereof, having a suspendable particle size spectrum in which at least 90% of the particles are smaller than 50 μ

m,

a physiologically inert dispersion medium in which the particles of active substance are suspended and in which dispersion medium the active substance has a solubility of less than 500 μ

g/ml, about 0.1 to about 5% by weight of highly dispersed silicon dioxide having a specific surface area of at least 50 m²/g, forming a three-dimensional siloid structure produced by adding the silicon dioxide to the dispersion medium with the action of shear forces characterised by a circumferential rotor speed of about 15 to 35 m/s, and

about 0.05 to about 2% by weight of a hydrophilic polymer, which polymer is soluble in the dispersion medium.

2. The pharmaceutical composition of matter as recited in claim 1 wherein the active substance is selected from the group consisting of piroxicam, tenoxicam, lomoxicam, meloxicam and the pharmaceutically acceptable salts thereof.

3. The pharmaceutical composition of matter as recited in claim 1 wherein the highly dispersed silicon dioxide is present in an amount of from about 0.5% to about 2% by weight.

4. The pharmaceutical composition of matter as recited in claim 1 wherein the hydrophilic polymer is a pharmaceutical-grade water soluble cellulose ether.

5. The pharmaceutical composition of matter as recited in claim 4 wherein the cellulose ether is present in an amount of from about 0.05% to about 0.5% by weight.

6. The pharmaceutical composition of matter as recited in claim 4 wherein the cellulose ether is selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose and hydroxypropyl methyl cellulose.

7. The pharmaceutical composition of matter as recited in claim 1 wherein at least about 50% of the particles of active substance are smaller than about 10 μ

m.

8. The pharmaceutical composition of matter as recited in claim 1 wherein the active substance is meloxicam and the dispersion medium is an aqueous buffer system with a pH in the range from about 2-4.

9. The pharmaceutical composition of matter as recited in claim 8 wherein the dispersion medium is a mixture of a physiologically acceptable aqueous buffer system with glycerol or with an aqueous solution of one or more sugar alcohols selected from the group consisting of xylitol, sorbitol and mannitol.

10. The pharmaceutical composition of matter as recited in claim 8 wherein the dispersion medium is a buffer system from the group consisting of

(a) sodium dihydrogen phosphate dihydrate/citric acid monohydrate,

(b) glycin/HCl,

(c) Na-citrate/HCl,

(d) K-hydrogen phthalate/HCl,

(e) citric acid/phosphate,

(f) citrate-phosphate-borate/HCl and

(g) Britton-Robinson buffer.

11. The pharmaceutical composition of matter as recited in claim 9 wherein the dispersion medium is a mixture of about 30 to about 50% aqueous sodium dihydrogen phosphate dihydrate/citric acid mono-hydrate buffer, about 10 to about 20% glycerol, about 10 to about 20% xylitol and about 20 to about 30% sorbitol or mannitol solution, the sorbitol or mannitol solution being an about 70% aqueous solution.

12. The pharmaceutical composition of matter as recited in claim 8 wherein the composition of matter comprises about 0.050 to about 3.000 g of meloxicam in about 118 g of pharmaceutical composition of matter.

13. The pharmaceutical composition of matter as recited in claim 1 further comprising a flavoring agent, a sweetener, a preservative or a mixture of such.