Valdecoxib compositions

• US 20020013357A1
• Filed: 12/06/2000
• Published: 01/31/2002
• Est. Priority Date: 12/08/1999
• Status: Abandoned Application

• Current Assignee: Pharmacia Corporation (Pfizer Inc.)
• Original Assignee: Pharmacia Corporation (Pfizer Inc.)
• Inventors: Kontny, Mark J., Nadkarni, Sreekant
• Application Number:
  US09/731,349
• Publication Number:
  US 20020013357A1
• Time in Patent Office: Days
• US Class Current: 514/406
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 : of the kidneys
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 17/10 : Anti-acne agents
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 : for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/12 : for cataracts
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 213/61 : Halogen atoms or nitro radicals
• CPC Class Codes: C07D 231/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 261/08 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 307/58 : One oxygen atom, e.g. butenolide
• CPC Class Codes: C07D 311/58 : other than with oxygen or sulphur atoms in position 2 or 4

Abstract

Pharmaceutical compositions are provided comprising particulate valdecoxib in an amount of about 1 mg to about 100 mg and one or more pharmaceutically acceptable excipients. The compositions are useful in treatment or prophylaxis of cyclooxygenase-2 mediated conditions and disorders.

Claims

1. A pharmaceutical composition comprising particulate valdecoxib in an amount of about 1 mg to about 100 mg per dose and one or more pharmaceutically acceptable excipients, wherein a single dose, upon oral administration to a fasting subject, provides a time course of blood serum concentration of valdecoxib having at least one of

(a) a time to reach a threshold concentration for therapeutic effect not greater than about 0.5 h after administration;

(b) a time to reach maximum concentration (T_max) not greater than about 5 h after administration; and

(c) a maximum concentration (C_max) not less than about 100 ng/ml.

2. The composition of claim 1 wherein the threshold concentration for therapeutic effect is about 20 ng/ml.

3. The composition of claim 2 wherein a single dose, upon oral administration to a fasting subject, provides a time course of blood serum concentration of valdecoxib having each of

(a) a time to reach a concentration of 20 ng/ml not greater than about 0.5 h after administration;

(b) a time to reach maximum concentration (T_max) not greater than about 3 h after administration; and

(c) a maximum concentration (C_max) not less than about 100 ng/ml.

4. The composition of claim 1 wherein the valdecoxib is in an amount of about 5 mg to about 40 mg per dose.

5. The composition of claim 1 that is a tablet wherein the excipients comprise one or more diluents in an amount of about 5% to about 99%, one or more disintegrants in an amount of about 0.2% to about 30%, one or more binding agents in an amount of about 0.5% to about 25%, and one or more lubricants in an amount of about 0.1% to about 10%, by weight of the composition.

6. The composition of claim 5 wherein the binding agent is pregelatinized starch.

7. The composition of claim 1 that is a tablet wherein the excipients comprise lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, pregelatinized starch and magnesium stearate.

8. The composition of claim 1 further comprising one or more opioid or analgesic drugs.

9. The composition of claim 1 wherein D₉₀ of the valdecoxib particles is less than about 75 μ

m.

10. The composition of claim 1 wherein the valdecoxib particles have a weight average particle size of about 1 to about 10 μ

m.

11. A process for preparing a composition of claim 5 comprising a step of wet granulating valdecoxib together with one or more diluents and a binding agent, a step of drying the resulting granules and a step of compressing the resulting dry granulate to form a tablet.

12. The process of claim 11 wherein, prior to the wet granulating step, valdecoxib is mixed under low shear with one or more diluents and a binding agent to form a premix for wet granulation;

and wherein, between the drying step and the compressing step, the granules are blended with a disintegrant and a lubricant to form a blend for tableting.

13. The process of claim 12 wherein the binding agent is pregelatinized starch.

14. The process of claim 13 wherein the diluents comprise lactose monohydrate and microcrystalline cellulose, the disintegrant is croscarmellose sodium and the lubricant is magnesium stearate.

15. The process of claim 11 wherein, prior to the wet granulating step, valdecoxib is mixed under high shear with a primary diluent, a first portion of a secondary diluent, a binding agent and a first portion of a disintegrant, to form a premix for wet granulation;

and wherein, between the drying step and the compressing step, the granules are blended with a second portion of the secondary diluent, a second portion of the disintegrant, and a lubricant, to form a blend for tableting.

16. The process of claim 15 wherein the binding agent is pregelatinized starch.

17. The process of claim 16 wherein the diluents comprise lactose monohydrate and microcrystalline cellulose, the disintegrant is croscarmellose sodium and the lubricant is magnesium stearate.

18. A method of treating a medical condition or disorder in a subject where treatment with a cyclooxygenase-2 inhibitor is indicated, comprising orally administering to the subject a composition of claim 1 once or twice a day.