''FIELD: pharmaceutics.
SUBSTANCE: group of inventions relates to a solid standard oral dosage form, including sacubitril and valsartan, suitable for use in sick children or other patients who need for the administration of low and individual doses or who have swallowing problems. The proposed minitablet contains a core and outer coating, where the core includes as an active ingredient therapeutically effective amount of sacubitril and valsartan in a molar ratio of 1:1; wherein the specified effective amount of the active ingredient is 3.534 mg of trisodium [3-((1S,3R)-1-biphenyl-4-ilmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-(S)-3'-methyl-2'-(pentanoyl{2''-(tetrazole-5-ylate)biphenyl-4'-ilmethyl}amino)butyrate] hemipentahydrate (LCZ696) per minitablet. The core includes the active ingredient in a concentration from 30 to 70 wt.% of the core weight before coating and pharmaceutically acceptable excipients, in % by the core weight before coating: from 35 to 45% of microcrystalline cellulose, from 3.5 to 5.5% of hydroxypropyl cellulose, from 1.5 to 3.5% of magnesium stearate, from 1.0 to 2.0% by weight of colloidal silicon dioxide, from 0.5 to 1.0% of talc. Outer coating is presented in the form of controlled release coating and/or protective film coating, where coating contains, in % by weight: from 55 to 60% of main butylated copolymer based on methacrylate, from 25 to 30% of talc, from 7.5 to 9% of stearic acid or Mg stearate, from 4 to 8% of sodium lauryl sulfate. In this case, the specified butylated copolymer is 1:2:1 copolymer formed from butyl methacrylate, (2-dimethylaminoethyl)methacrylate and methyl methacrylate. The minitablet has a size from 1 to 3 mm. An oral capsule containing a certain number of minitablets is also proposed. The minitablet is characterized by the size, acceptability and taste properties desirable for use in the pediatric group of patients, while maintaining bioavailability comparable to the currently available medicinal product, and it is intended, in particular, for the treatment of heart failure in such patients.
EFFECT: use of a minitablet ensures the flexibility of dosing.
9 cl, 3 tbl, 5 ex
