SOLID COMPOSITIONS BASED ON BETAHISTINE FOR ORAL ADMINISTRATION WITH NON-PULSATING PROLONGED RELEASE Russian patent published in 2022 - IPC A61K9/20 A61K31/4402 A61K47/00 

FIELD: medicine.

SUBSTANCE: group of inventions relates to the field of medicine, namely, to a solid composition for oral administration with non-pulsating prolonged release for 24 hours, containing certain amount of betahistine or its pharmaceutically acceptable salt, equivalent to 48 mg of betahistine dihydrochloride, together with one or several pharmaceutically acceptable auxiliary substances or carriers, where the composition is characterized by a dissolution profile, according to which: no more than 30% by weight of betahistine is dissolved in 1 hour; from 35 to 45% by weight of betahistine is dissolved in 2 hours; from 46 to 60% by weight of betahistine is dissolved in 4 hours; from 61 to 80% by weight of betahistine is dissolved in 8 hours; from 81 to 97% by weight of betahistine is dissolved in 16 hours, and from 98 to 100% by weight of betahistine is dissolved in 24 hours, where pharmaceutically acceptable auxiliary substances or carriers provide one or several agents forming a hydrophilic matrix, where the agent forming a hydrophilic matrix is a mixture of hydroxypropyl methylcellulose and carrageenan in a weight ratio from 3:1 to 12:1. The group of inventions also relates to a preparation method, which provides: (a) preparation of a solution of betahistine or its pharmaceutically acceptable salt in a polar solvent selected from a group of (C₁-C₄)alkyl-CO-(C₁-C₄)alkyl, (C₁-C₄)alkyl)-COO-(C₁-C₄)alkyl, water and a mixture thereof; (b) sieving and mixing of one or several diluents, one or several stabilizers and optionally one or several binders to produce a mixture; (c) granulation of the mixture from the stage (b) by adding the solution from the stage (a) to obtain wet granules; (d) drying of wet granules obtained at the stage (c) to obtain dried granules; (e) mixing of dried granules obtained at the stage (d) with one or several agents forming a hydrophilic matrix to obtain a mixture; and (f) pressing of the mixture obtained at the stage (e) to form tablets.

EFFECT: group of inventions provides the provision of a solid composition for oral administration, providing a lower index of the maximum betahistine concentration in blood (Cmax) and a higher index of the minimum betahistine concentration in blood (Cmin), as well as betahistine metabolite – 2-PAA – compared to the administration twice a day of a solid composition for oral administration with immediate release, which reduces fluctuations in its concentration in plasma and, therefore, eliminates side effects of insufficient or excessive dosage, associated with the administration of at least two separate dosage forms with immediate release or a separate dosage form in the form of a set of particles, containing dosage forms with immediate and delayed release.

9 cl, 1 dwg, 5 tbl, 3 ex