Claims for Patent: 6,656,482

Summary for Patent: 6,656,482

Title:	Spill resistant pharmaceutical system
Abstract:	A spill-resistant pharmaceutical formulation for oral administration from a squeezable container comprises a pharmaceutical agent in a suitable vehicle comprising a liquid base and a thickening agent, the formulation consisting of mutually compatible components and having the following properties: a viscosity within the range of about 7500 to about 12,500 cps using a Brookfield Viscometer with a `C` spindle with Helipath movement at a spindle speed of 10 rpm and 20-25.degree. C., a viscometric yield value of a semi-solid, a spill-resistant consistency permitting the composition to be squeezed by light manual pressure through a channel, to spread in a spoon bowl sufficiently quickly for accurate measurement, and to remain in the spoon bowl without spilling on spoon inversion, tilting at 90 degrees, and vibration, homogeneity such that the components do not separate under conditions of use, and a storage stability such that the foregoing properties are retained for at least two years shelf life. A method for producing a formulation for a spill-resistant pharmaceutical composition comprises combining a per-unit dose effective amount of a pharmaceutical agent with suitable vehicle components comprising a liquid base and a thickening agent, and testing the formulation for acceptance criteria.
Inventor(s):	Mehta; Rakesh (Nanuet, NY), Moros; Dan (Larchmont, NY)
Assignee:	Taro Pharmaceutical Industries Ltd. (Haifa Bay, IL)
Application Number:	10/052,462
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,656,482
Patent Claims:	1. A ready-to-use pharmaceutical delivery system comprising a squeezable container containing a formulation from which a unit dose of the formulation may be squeezed, the formulation comprising a pharmaceutical agent in a vehicle comprising a liquid base and a thickening agent, the formulation consisting of mutually compatible components, wherein said thickening agent comprises components selected from the group consisting of cellulose derivatives in an amount of less than about 2 weight % by volume, and water-soluble carboxyvinyl polymer in an amount less than 1 weight % by volume, the formulation having the following properties: an initial viscosity within the range of about 5,000 cps to about 12,500 cps; a viscometric yield value of a semi-solid; a spill resistant consistency permitting the formulation to be squeezed by light manual pressure through a channel of about 1 to about 5 mm, to spread in a spoon bowl sufficiently quickly for accurate measurement, and to remain in the spoon bowl without spilling; homogeneity wherein the components do not separate under conditions of use; and storage stability. 2. The system of claim 1, wherein the container contains a single dose of the formulation. 3. The system of claim 1, wherein the container contains multiple doses of the formulation. 4. The system of claim 3, further comprising a spoon bowl receptacle attachable to the container. 5. A method for using the pharmaceutical delivery system of claim 1, comprising: obtaining a container according to claim 1, squeezing the container, dispensing a unit dose of the formulation into a spoon, allowing a patient to consume the formulation from the spoon. 6. The system of claim 1, wherein the formulation has a viscosity between about 7500 and about 25,000 cps after storage for three months at a temperature of 40 degrees C. and 75% humidity. 7. The system of claim 6, wherein the formulation has a viscosity between about 7500 and about 12,500 cps after storage. 8. The system of claim 1, wherein the viscosity is at least about 7,000 cps. 9. The system of claim 1, wherein the viscosity is at least about 7,500 cps. 10. The system of claim 1, wherein the storage stability extrapolates to at least two years shelf life at room temperature. 11. The system of claim 1, wherein after storage for three months at elevated temperature, the viscosity remains within a range of 50% less to 100% more than the initial viscosity. 12. The system of claim 1, the formulation spreading as quickly as honey, and having spill resistance greater than honey. 13. The system of claim 1, the formulation spreading to the edge of a spoon within about five seconds. 14. The system of claim 1, wherein the formulation is readily consumed from a spoon bowl. 15. The system of claim 1, wherein the thickening agent comprises from about 0.25 to less than 1 weight % water-soluble carboxyvinyl polymer. 16. The system of claim 1, wherein the thickening agent comprises water-soluble carboxyvinyl polymer in an amount of from about 0.25 to about 0.5 weight % by volume. 17. The system of claim 1, wherein the thickening agent comprises sodium carboxymethylcellulose in an amount of about 0.9% and microcrystalline cellulose in an amount of about 0.9%. 18. The system of claim 1, wherein the thickening agent comprises cellulose derivatives in an amount of less than about 2 weight % by volume, and the formulation further comprises glycerin and sorbitol as a solution of about 70% in water, the combined concentration of glycerin and sorbitol solution being about 40%. 19. The system of claim 1, wherein the thickening agent comprises cellulose derivatives in an amount of less than about 2 weight % by volume, and the liquid base comprises propylene glycol in an amount of from about 10 to about 85 weight % by volume. 20. The system of claim 1, wherein the pharmaceutical agent is selected from the group consisting of an analgesic, non-steroidal anti-inflammatory, antihistamine, cough suppressant, expectorant, bronchodilator, anti-infective, CNS active drug, cardiovascular drug, antineoplastic, cholesterol-lowering drug, anti-emetic, vitamin, mineral supplement and fecal softener. 21. The system of claim 1, wherein the pharmaceutical agent is selected from the group consisting of acetaminophen, aspirin, ibuprofen, diphenhydramine, dextromethorphan, guafenesin, pseudoephedrine, carbidopa, levodopa, terfenadine, ranitidine, ciprofloxacin, triazolam, fluconazole, propranolol, acyclovir, fluoxetine, enalapril, diltiazem, lovastatin and a pharmaceutically acceptable salt or ester thereof. 22. The system of claim 1, wherein the liquid base comprises glycerin. 23. The system of claim 1, wherein the liquid base comprises glycerin and sorbitol. 24. The system of claim 1, wherein the liquid base comprises from about 30% to about 50% glycerin. 25. The system of claim 24, wherein the liquid base further comprises propylene glycol in an amount up to about 25 weight % by volume. 26. The system of claim 1, wherein the liquid base comprises propylene glycol. 27. The system of claim 1, wherein the formulation remains in the spoon bowl without spilling for at least about one second on spoon tilting. 28. The system of claim 1, wherein the formulation remains in the spoon bowl without spilling for less than about 20 seconds on spoon tilting. 29. The system of claim 1, wherein the formulation remains in the spoon bowl without spilling for at least about 30 seconds upon spoon vibration. 30. The system of claim 1, wherein the formulation remains in the spoon bowl without spilling for about 20-30 seconds on spoon inversion. 31. A ready-to-use pharmaceutical delivery system comprising a squeezable container containing a formulation from which a unit dose of the formulation may be squeezed, the formulation comprising a pharmaceutical agent in a vehicle comprising a liquid base comprising from about 30% to about 50% glycerin, and a thickening agent, the formulation consisting of mutually compatible components and having the following properties: an initial viscosity within the range of about 5,000 cps to about 12,500 cps; a viscometric yield value of a semi-solid; a spill-resistant consistency permitting the formulation to be squeezed by light manual pressure through a channel of about one to about five mm, to spread in a spoon bowl sufficiently quickly for accurate measurement; homogeneity wherein the components do not separate under conditions of use; and storage stability for at least three months of storage at elevated temperature, with viscosity remaining within a range of 50% less to 100% more than the initial viscosity. 32. The system claim 31, wherein said thickening agent comprises components selected from the group consisting of cellulose derivatives in an amount of from about 0.9 to 2.5 weight %, and water-soluble carboxyvinyl polymer in an amount less than 1 weight % by volume. 33. The system of claim 31, wherein the liquid base comprises about 50% glycerin and the thickening agent comprises water-soluble carboxyvinyl polymer in an amount of from about 0.25 to about 1 weight % by volume. 34. The system of claim 31, wherein the liquid base further comprises propylene glycol. 35. A ready-to-use pharmaceutical delivery system comprising a squeezable container containing a formulation from which a unit dose of the formulation may be squeezed, the formulation comprising a pharmaceutical composition comprising: a water-soluble carboxyvinyl polymer in an amount of 1.0% by weight or less; a liquid base comprising glycerin and/or propylene glycol; and a pharmaceutical agent, the composition being a homogeneous semi-solid and dispensable from a squeezable container, and having a viscosity of less than about 12,000 cps. 36. The system of claim 35, wherein the water-soluble carboxyvinyl polymer is in an amount of from about 0.25% to about 0.5% by weight. 37. The system of claim 35, wherein the liquid base comprises glycerin in an amount greater than 15%. 38. The system of claim 35, wherein the formulation, when squeezed through a channel into a spoon, remains in the spoon without spilling for at least about one second on spoon tilting. 39. The system of claim 35, wherein the formulation, when squeezed through a channel into a spoon, remains in the spoon without spilling for less than about 20 seconds on spoon tilting. 40. The system of claim 35, wherein the formulation, when squeezed through a channel into a spoon, remains in the spoon without spilling for at least about 30 seconds upon spoon vibration. 41. The system of claim 35, wherein the formulation, when squeezed through a channel into a spoon, remains in the spoon without spilling for about 20-30 seconds on spoon inversion.