Pharmaceutical suspension
View Patent ↗The present invention is directed to the provision of a pharmaceutical suspension. The suspension includes high molecular weight polyethylene glycol as a suspending agent. The suspension also typically includes an antimicrobial agent (e.g., polymeric quaternary ammonium compound), an antimicrobial system (e.g., borate/polyol complex system) or both. The suspension has been found particularly useful as an ophthalmic suspension, but can be used in other instances as well.
1. A pharmaceutical suspension, comprising:
an aqueous solution that includes high molecular weight polyethylene glycol, polyethylene oxide or both as a suspending agent, the high molecular weight polyethylene glycol, when included, having a molecular weight that is at least 2000; and
a therapeutic agent that is suspended by the high molecular weight polyethylene glycol, polyethylene oxide or both within the solution wherein:
i. the polyethylene oxide, when included in the suspension, is in the suspension at a concentration that is at least 0.5 w/v % but less that 10 w/v % and has a molecular weight of 100,000 to 8,000,000; and
ii. the polyethylene glycol, when included in the suspension, is in the suspension at a concentration that is at least 15 w/v % but less that 50 w/v %.
2. A pharmaceutical suspension as in claim 1 wherein the therapeutic agent is selected from roscovitine, brinzolamide, tandospirone, anecortave acetate, bradykinin related agents, dexamethasone, nepafenac, any combination thereof.
3. A pharmaceutical suspension as in claim 1 further comprising a second therapeutic agent which is soluble or solubilized in the formulation.
4. A pharmaceutical suspension as in claim 3 wherein the second therapeutic agent is travoprost, latanoprost, bimatoprost, dorzolamide, timolol, brimonidine, moxifloxacin or a combination thereof.
5. A pharmaceutical suspension as in claim 1 wherein the suspension has a degree of flocculation of at least 10.
6. A pharmaceutical suspension as in claim 1 wherein the suspension is an ophthalmic, otic or nasal suspension.
7. A pharmaceutical suspension as in claim 6 wherein the suspension is an ophthalmic suspension.
8. A pharmaceutical suspension as in claim 1 wherein the suspension is substantially free of any non-polymeric quaternary ammonium compound, particularly BAK.
9. A pharmaceutical suspension as in claim 1 further comprising an antimicrobial agent.
10. A pharmaceutical suspension as in claim 9 wherein the antimicrobial agent includes polymeric quaternary ammonium compound.
11. A pharmaceutical suspension as in claim 10 further comprising borate, polyol or both.
12. A pharmaceutical suspension as in claim 11 wherein the borate is boric acid.
13. A pharmaceutical suspension as in either claim 12 wherein the polyol is selected from glycerol, propylene glycol, mannitol, sorbitol or any combination thereof and the polyol forms a borate/polyol complex in the suspension.
14. A pharmaceutical suspension as in claim 1 wherein the concentration of polyethylene oxide, when included in the suspension, is at least 1.0 w/v %.
15. A pharmaceutical suspension as in claim 1 wherein the high molecular weight polyethylene glycol has a molecular weight that is at least 10,000.
16. A pharmaceutical suspension as in claim 1 wherein the viscosity of the suspension is greater than 15 cps but no greater than 1000 cps wherein the viscosity of the suspension is measured at a high shear rate of 46 sec-1 at room temperature.
17. A pharmaceutical suspension as in claim 1 wherein the density of the suspension is greater than 1.015 cps.
18. A pharmaceutical suspension as in claim 1 wherein the suspension includes a surfactant.
19. A pharmaceutical suspension as in claim 18 wherein the surfactant is tyloxapol.
20. A suspension as in claim 1 wherein the volume mean diameter particle size of any suspended or suspendable therapeutic agent in the suspension is typically at least 0.1 μm but no greater than 20 μm.
21. A pharmaceutical suspension, comprising:
an aqueous solution that includes high molecular weight polyethylene glycol, polyethylene oxide or both as a suspending agent, the high molecular weight polyethylene glycol, when included, having a molecular weight that is at least 2000; and
therapeutic agent that is suspended by the high molecular weight polyethylene glycol, polyethylene oxide or both within the solution;
wherein the suspension has a degree of flocculation of at least 10;
wherein the suspension is an ophthalmic, otic or nasal suspension;
wherein the viscosity of the suspension is greater than 15 cps but no greater than 1000 cps wherein the viscosity of the suspension is measured at a high shear rate of 46 sec-1 at room temperature;
wherein the polyethylene oxide, when included in the suspension, is in the suspension at a concentration that is at least 0.5 w/v % but less that 10 w/v % and has a molecular weight of 100,000 to 8,000,000; and
wherein the polyethylene glycol, when included in the suspension, is in the suspension at a concentration that is at least 15 w/v % but less that 50 w/v %.
22. A pharmaceutical suspension as in claim 21 wherein the suspension is an ophthalmic suspension.
23. A pharmaceutical suspension as in claim 22 wherein the concentration of polyethylene oxide, when included in the suspension, is at least 1.0 w/v %.
24. A pharmaceutical suspension as in claim 1 wherein the suspending agent consists essentially of polyethylene oxide, the polyethylene glycol or a combination thereof.
25. A pharmaceutical suspension as in claim 21 wherein the suspending agent consists essentially of polyethylene oxide, the polyethylene glycol or a combination thereof.
26. A pharmaceutical suspension as in claim 25 wherein the suspension includes a polymeric quaternary ammonium compound.