Formulation of diclofenac
The present invention relates to methods for producing particles of diclofenac using dry milling processes as well as compositions comprising diclofenac, medicaments produced using diclofenac in particulate form and/or compositions, and to methods of treatment of an animal, including man, using a therapeutically effective amount of diclofenac administered by way of said medicaments.
1. A method for producing a composition comprising nanoparticles of diclofenac acid, comprising:
dry milling a composition comprising diclofenac acid, lactose and sodium lauryl sulfate in a mill containing a plurality of milling bodies for a time period sufficient to produce a composition comprising nanoparticles of diclofenac acid having a median particle size on a particle volume basis between 1,000 nm and 25 nm; and processing the composition comprising nanoparticles of diclofenac acid into a unit dosage pharmaceutical composition containing 18 mg of diclofenac acid, wherein the unit dosage pharmaceutical composition, when tested in vitro by USP Apparatus I (Basket) method of U.S. Pharmacopoeia at 100 rpm at 37 °C. in 900 ml of 0.05% sodium lauryl sulfate in citric acid solution buffered to pH 5.75, has a dissolution rate of diclofenac acid such that at least 91%, by weight, is released by 45 minutes.
2. The method of claim 1 wherein the processing comprises combining the composition comprising nanoparticles of diclofenac acid with at least one pharmaceutically acceptable excipient or carrier.
3. The method of claim 2 wherein the processing comprises combining the composition comprising nanoparticles of diclofenac acid with microcrystalline cellulose, croscarmellose sodium, and sodium stearyl fumarate.
4. The method of claim 1 wherein the unit dosage pharmaceutical composition comprises a hard gelatin capsule.
5. The method of claim 1 or 4 wherein the unit dosage pharmaceutical composition has a dissolution rate of diclofenac acid such that at least 91%, by weight, is released by 30 minutes.
6. The method of claim 1 or 4 wherein the unit dosage pharmaceutical composition has a dissolution rate of diclofenac acid such that at least 91%, by weight, is released by 15 minutes.
7. The method of claim 1 or 4 wherein the unit dosage pharmaceutical composition has a dissolution rate of diclofenac acid such that at least 94%, by weight, is released by 45 minutes.
8. The method of claim 1 or 4 wherein the unit dosage pharmaceutical composition has a dissolution rate of diclofenac acid such that at least 94%, by weight, is released by 30 minutes.
9. The method of claim 1 wherein the unit dosage pharmaceutical composition is a filled capsule.
10. A method for producing a composition comprising nanoparticles of diclofenac acid, comprising:
dry milling a composition comprising diclofenac acid, lactose and sodium lauryl sulfate in a mill containing a plurality of milling bodies for a time period sufficient to produce a composition comprising nanoparticles of diclofenac acid having a median particle size on a particle volume basis between 1,000 nm and 25 nm; and processing the composition comprising nanoparticles of diclofenac acid into a unit dosage pharmaceutical composition containing 35 mg of diclofenac acid, wherein the unit dosage pharmaceutical composition, when tested in vitro by USP Apparatus I (Basket) method of U.S. Pharmacopoeia at 100 rpm at 37 °C. in 900 ml of 0.05% sodium lauryl sulfate in citric acid solution buffered to pH 5.75, has a dissolution rate of diclofenac acid such that at least 82%, by weight, is released by 45 minutes.
11. The method of claim 10 wherein the processing comprises combining the composition comprising nanoparticles of diclofenac acid with at least one pharmaceutically acceptable excipient or carrier.
12. The method of claim 11 wherein the processing comprises combining the composition comprising nanoparticles of diclofenac acid with microcrystalline cellulose, crosscarmellose sodium, and sodium stearyl fumarate.
13. The method of claim 10 wherein the unit dosage pharmaceutical composition comprises a hard gelatin capsule.
14. The method of claim 10 or 13 wherein the unit dosage pharmaceutical composition has a dissolution rate of diclofenac acid such that at least 82%, by weight, is released by 30 minutes.
15. The method of claim 10 or 13 wherein the unit dosage pharmaceutical composition has a dissolution rate of diclofenac acid such that at least 82%, by weight, is released by 15 minutes.
16. The method of claim 10 or 13 wherein the unit dosage pharmaceutical composition has a dissolution rate of diclofenac acid such that at least 95%, by weight, is released by 45 minutes.
17. The method of claim 10 or 13 wherein the unit dosage pharmaceutical composition has a dissolution rate of diclofenac acid such that at least 95%, by weight, is released by 30 minutes.
18. The method of claim 10 wherein the unit dosage pharmaceutical composition is a filled capsule.