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CN-121971393-A - Betahistine mesylate tablet composition and preparation method thereof

CN121971393ACN 121971393 ACN121971393 ACN 121971393ACN-121971393-A

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly discloses a betahistine mesylate tablet composition and a preparation method thereof, wherein the composition comprises a drug-containing resin compound formed by betahistine mesylate and high polymer resin and pharmaceutical auxiliary materials, the mass ratio of the drug to the resin is 1:6-1:1, preferably 1:3-1:2, and the resin is sodium polystyrene sulfonate. The preparation method comprises mixing the medicine with resin in water, drying to obtain compound, and tabletting with disintegrating agent, filler, etc. The core of the invention is that the resin compound is used for physically isolating the medicine, so that the generation of the cancerogenic substance N-nitrosobetahistine is effectively inhibited from the source, and the stability problem caused by using oily auxiliary materials in the prior art is solved. The obtained tablet has rapid and complete dissolution, uniform content, less related substances, and remarkably slowed down nitrosamine growth under the condition of accelerated stability, and simple and convenient process, is suitable for industrial production, and is used for treating dizziness or balance disorder.

Inventors

  • CAI XIANGJIE
  • GAI SHUCHANG
  • LIU YANG
  • QI XINGXING
  • DONG XIJUAN
  • WANG JINBAO
  • JIA RUOXIN

Assignees

  • 河北龙海药业股份有限公司

Dates

Publication Date
20260505
Application Date
20260203

Claims (10)

  1. 1. The betahistine mesylate tablet composition is characterized by comprising a drug-containing resin compound formed by betahistine mesylate and high polymer resin and pharmaceutically acceptable auxiliary materials, wherein the mass ratio of the betahistine mesylate to the high polymer resin is 1:6-1:1.
  2. 2. The tablet composition according to claim 1, wherein the high molecular polymer resin is selected from sodium polystyrene sulfonate.
  3. 3. The tablet composition according to claim 1, wherein the mass ratio of the betahistine mesylate to the high molecular polymer resin is 1:3-1:2.
  4. 4. The tablet composition of claim 1, wherein the pharmaceutically acceptable excipients comprise at least one of a disintegrant, a filler, a binder, and a lubricant.
  5. 5. The method for preparing the betahistine mesylate tablet composition according to any one of claims 1 to 4, comprising the steps of: (1) Dissolving betahistine mesylate in water, adding high molecular polymer resin, stirring in a water bath at 60 ℃ for 1-4 hours, standing, discarding supernatant, cleaning sediment, and drying until the water content is less than or equal to 5.0%, thus obtaining a drug-containing resin compound; (2) Mixing the resin compound with pharmaceutically acceptable auxiliary materials, and making into tablet by compression process.
  6. 6. The method according to claim 5, wherein the drying temperature in step (1) is 60 to 80 ℃.
  7. 7. The method according to claim 5, wherein the compression process in step (2) is selected from one of powder direct compression, wet granulation or dry granulation.
  8. 8. A tablet, characterized in that it is made from the tablet composition according to any one of claims 1 to 4 or the preparation method according to any one of claims 5 to 7.
  9. 9. The tablet of claim 8, wherein the tablet has a substantially lower increase in N-nitrosobetahistine content under accelerated stability test conditions than a control tablet without the high molecular polymer resin.
  10. 10. Use of a tablet composition according to any one of claims 1 to 4 or a tablet according to any one of claims 8 to 9 for the preparation of a medicament for the treatment of dizziness or balance disorders.

Description

Betahistine mesylate tablet composition and preparation method thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations, and particularly discloses a betahistine mesylate tablet composition and a preparation method thereof. Background Betahistine mesylate, a drug for treating dizziness and balancing disorders developed and used by japan kava alone, is a histamine-based drug that exerts a histamine-like effect by agonizing the histamine H1 receptor. The medicine can specifically increase blood circulation in brain and brain stem and microcirculation in inner ear, eliminate endolymphedema, treat dizziness and vertigo caused by various diseases, and is mainly used for treating dizziness and balance disorder accompanied by Meniere disease and peripheral vertigo, and has remarkable curative effect. The structural formula of the betahistine mesylate contains a secondary amine structure, so that the betahistine mesylate is easy to generate nitrosation reaction with amine substances (such as unreacted methylamine) remained in a synthesis system or nitrite introduced in the process, and cancerogenic N-nitrosobetahistine is generated. The international agency for research on cancer (IARC) has classified N-nitrosamines as class 1 carcinogens and is extremely harmful. In CN120478348A, betahistine hydrochloride, conjugated linoleic acid, glycerol and other auxiliary materials are prepared into a preparation, and the conjugated double bond of the conjugated linoleic acid can be specifically combined with nitrite to block the generation of nitrosamine, so that the generation of nitrosamine impurities is reduced. However, when the preparation is used for oral solid preparation in the embodiment of the invention, when the preparation is prepared into tablets or hard capsules, the oily auxiliary materials are unfavorable for production and storage, migration or oil spots on the surface can occur, and the quality of the product is reduced. Other solid preparations for reducing nitrosamine impurities and preparation methods have been reported. Disclosure of Invention Aiming at the defects of the prior art, the invention discloses a betahistine mesylate tablet composition and a preparation method thereof. The defects of the solution can be avoided, the product quality is ensured to be higher, the nitrosamine impurity is kept at a low level in the preparation and stability processes, and meanwhile, the process is simple, so that the method is suitable for commercial mass production. The aim of the invention is achieved by the following technical scheme. The betahistine mesylate tablet composition comprises a drug-containing resin compound formed by betahistine mesylate and high polymer resin and pharmaceutically acceptable auxiliary materials, wherein the mass ratio of the betahistine mesylate to the high polymer resin is 1:6-1:1. Further, in the above composition, the high polymer resin is selected from sodium polystyrene sulfonate. Further, in the composition, the mass ratio of the betahistine mesylate to the high polymer resin is 1:3-1:2. Further, in the above composition, the pharmaceutically acceptable auxiliary materials include at least one of a disintegrating agent, a filler, a binder and a lubricant. Disintegrants include, but are not limited to, crospovidone (PVPP), sodium carboxymethyl starch (CMS-Na), low-substituted hydroxypropyl methylcellulose (L-HPC), or sodium croscarmellose (CCNa), and the like. Fillers include, but are not limited to, mannitol, xylitol, sorbitol, maltose, erythritol xian, microcrystalline cellulose, silicified microcrystalline cellulose, lactose, sucrose, dextrin, starch, pregelatinized starch, and the like. Binders include, but are not limited to, starch, dextrin, povidone (PVP), copovidone, hydroxypropyl cellulose (HPC), and hydroxypropyl methylcellulose (HPMC). Lubricants include, but are not limited to, magnesium stearate, calcium stearate, glyceryl monostearate, sodium stearyl fumarate, talc, and the like. The invention also discloses a preparation method of the betahistine mesylate tablet composition, which comprises the following steps: (1) Dissolving betahistine mesylate in water, adding high molecular polymer resin, stirring in a water bath at 60 ℃ for 1-4 hours, standing, discarding supernatant, cleaning sediment, and drying until the water content is less than or equal to 5.0%, thus obtaining a drug-containing resin compound; (2) Mixing the resin compound with pharmaceutically acceptable auxiliary materials, and making into tablet by compression process. Further, in the preparation method, in the step (1), the drying temperature is 60-80 ℃. Further, in the preparation method, the compression process in the step (2) is selected from one of powder direct compression, wet granulation or dry granulation. The invention also discloses a tablet, which is prepared from the tablet composition according to any one of the above or the preparation meth