Claims for Patent: 10,722,471

Summary for Patent: 10,722,471

Title:	Galenic formulations of organic compounds
Abstract:	The present invention relates to a solid unit oral dosage form comprising sacubitril and valsartan in a 1:1 molar ratio, preferably in the form of the so-called angiotensin receptor neprilysin inhibitor (ARNI) LCZ696, which is a complex salt hydrate of sacubitril, valsartan, and sodium ions, appropriate for use in pediatrics or other patients where low and individual dosing is required or who encounter problems with swallowing e.g. as a result of a disease or because of age, to the manufacture of said solid dosage form and to invention embodiments relating to therapy using said dosage form.
Inventor(s):	Winzenburg Gesine, Trueby Bernd, Chen Fabian, Ayalasomayajula Surya Prakash, Bush Christopher, Berkhin Masha
Assignee:	Novartis AG
Application Number:	US16074579
Patent Claims:	1. A minitablet for oral administration having a core and an outer coating and having a diameter of 1 mm to 4 mm , wherein the core comprises:an amount of sacubitril and valsartan in a 1:1 molar ratio as an active ingredient; andat least one pharmaceutically acceptable excipient,wherein the amount is about 2 mg to about 5 mg, corresponding to a respective combined amount of valsartan (free acid) and sacubitril (free acid) in a 1:1 molar ratio,wherein the outer coating is in a form of a controlled release and/or a protective film-coating, andwherein the film-coating has a basic butylated methacrylate copolymer content of 50% to 70% by weight of the film coating.2. The minitablet according to claim 1 , wherein the core comprises trisodium [3-((1S claim 1 ,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1 -butylcarbamoyl)propionate-(S)-3′-methyl-2′-(pentanoyl{2″-(tetrazol-5-ylate) biphenyl-4′-ylmethyl}amino)butyrate] hemipentahydrate as the active ingredient.3. The minitablet according to claim 1 , wherein the diameter of the minitablet is 1 mm to 3 mm.4. The minitablet according to claim 1 , wherein the minitablet contains 3.125 mg of the active ingredient.5. The minitablet according to claim 1 , wherein the mini-tablet contains about 3 mg to about 4 mg of trisodium [3-((1S claim 1 ,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1 -butylcarbamoyl)propionate-(S)-3′-methyl-2′-(pentanoyl{2″-(tetrazol-5-ylate) biphenyl-4′-ylmethyl}amino)butyrate] hemipentahydrate.6. The minitablet according to claim 1 , wherein the film-coating comprises a basic butylated methacrylate copolymer formed from monomers selected from butyl methacrylate claim 1 , (2-dimethylaminoethyl)methacrylate claim 1 , and methyl methacrylate.7. The minitablet according to claim 6 , wherein the basic butylated methacrylate copolymer is a 1:2:1 copolymer formed from butyl methacrylate claim 6 , (2-dimethylaminoethyl)-methacrylate and methyl methacrylate.8. The minitablet according to claim 1 , wherein the film-coating further comprises sodium lauryl sulphate claim 1 , stearic acid claim 1 , and talcum.9. The minitablet according to claim 1 , wherein the film-coating further comprises talcum at a content of 20% to 40% by weight of the film-coating claim 1 , stearic acid or magnesium stearate at a content of 5% to 10% by weight of the film-coating claim 1 , and sodium lauryl sulphate at a content of 4% to 8% by weight of the film-coating.10. The minitablet according to claim 1 , wherein a weight of the film-coating is about 4% to about 8% based on a total weight of the minitablet.11. The minitablet according to claim 1 , wherein a content of the active ingredient in the core is 30% to 70% by weight.12. The minitablet according to claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises (i) microcrystalline cellulose claim 1 , (ii) hydroxypropylcellulose claim 1 , (iii) magnesium claim 1 , calcium claim 1 , or aluminum stearate claim 1 , (iv) anhydrous colloidal silica (colloidal silicon dioxide) claim 1 , and (v) talc.13. The minitablet according to claim 12 , wherein microcrystalline cellulose is present in an amount of 35% to 45% by weight claim 12 , hydroxypropylcellulose is present in an amount of 2% to 8% by weight claim 12 , magnesium stearate is present in an amount of 1.0 to 5.0% by weight claim 12 , colloidal silicon dioxide is present in an amount of from 1.0% to 2.0% by weight claim 12 , and talc is present in an amount of from 0.5 to 1.0% by weight claim 12 , wherein the % by weight refers to the % by weight of the core.14. A combination of minitablets and a dispenser claim 1 , wherein the minitablets comprise the minitablet according to .15. A capsule containing 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 9 claim 1 , 10 claim 1 , 11 claim 1 , 12 claim 1 , 13 claim 1 , 14 claim 1 , 15 claim 1 , 16 claim 1 , 17 claim 1 , 18 claim 1 , 19 claim 1 , or 20 minitablets claim 1 , wherein the minitablets comprise the minitablet according to .16. A method of treating heart failure in a pediatric patient claim 1 , comprising administering to the pediatric patient in need of such treatment the minitablet according to .17. A method of treating chronic heart failure claim 1 , hypertension claim 1 , angina claim 1 , myocardial infarction claim 1 , atherosclerosis claim 1 , diabetic nephropathy claim 1 , diabetic cardiac myopathy claim 1 , renal insufficiency claim 1 , peripheral vascular disease claim 1 , left ventricular hypertrophy claim 1 , cognitive dysfunction or stroke in a patient where low and individual dosing is required or who encounter problems with swallowing claim 1 , comprising administering to the patient the minitablet according to .18. The minitablet according to claim 1 , wherein the film-coating dissolves only at a pH of 5 or lower.