Lansoprazole sodium submicron emulsion freeze-drying preparation

Abstract

The invention provides a method for preparing Lansoprazole sodium submicron emulsion freeze-drying preparation and the product thereof. The method includes the following steps: (1) Lansoprazole and sodium hydroxide are dissolved together in water, biodegradable polymer is dissolved in and mixed and stirred with organic solvent to form W / O type emulsion; (2) stabilizing agent and apodemal agent are dissolved in water, and the obtained solution is added to the W / O type emulsion to be stirred to form W / O / W type emulsion; and (3) the W / O type emulsion is added to the emulsifying agent aqueous solution and stirred into the same at room temperature, and the submicron emulsion freeze-drying preparation is obtained after the operations of pressure reduction for organic solvent evaporation, eccentric separation, water rinsing, freezing and drying are performed.

Description

technical field [0001] The invention relates to a submicron emulsion preparation of lansoprazole sodium, in particular to a submicroemulsion freeze-dried preparation of lansoprazole sodium and a preparation method thereof. Background technique [0002] Lansoprazole sodium, its chemical name is: 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]-sulfinyl] -1H-benzimidazole sodium salt, molecular formula C 16 h 13 f 3 N 3 NaO 2 S, molecular weight 391.34, structural formula: [0003] [0004] It is a new type of drug that inhibits gastric acid secretion. It acts on the H+-K+-ATPase of gastric parietal cells, so that the H+ of parietal cells cannot be transported to the stomach, so that the amount of gastric acid in gastric juice is greatly reduced. It is clinically used for ten The treatment of duodenal ulcer, gastric ulcer, reflux esophagitis, and Zollinger-Ellison syndrome (gastrinoma) has remarkable curative effect, and has inhibitory effect on Helicobacter ...

AI Technical Summary

Problems solved by technology

[0005] Lansoprazole sodium is unstable under acidic conditions, is easily destroyed in gastric acid, is slowly absorbed orally after being made into tablets or capsules, and has low bioavailability, so it needs to be made into injections, but because Lansoprazole The stability of the azole solution is very poor, and it cannot be sterilized by high temperature, and only the freeze-drying method can be used to prepare injections

However, during the development, it was found that the lansoprazole freeze-dried powder injection prepared by the common preparation method was reconstituted with obvious foreign matter, and the insoluble particles were unqualified

[0006] The disclosed lansoprazole sodium freeze-dried powder injection of CN1810224A adopts meglumine as stabilizer, but only contains a basic group in the meglumine structure, although certain buffering effect is arranged, but not strong enough, to make lansoprazole The medicinal solution prepared by injection will precipitate and crystallize after being placed at room temperature for no more than 4 hours, so it cannot be used for injection

CN1279909C discloses adding basic amino acid to stabilize lansoprazole sodium, and the storage effect is still unsatisfactory

In CN1660092A, antioxidants commonly used in this field are added, but the difficult problem of precipitation and crystallization that is prone to occur in the preparation process is not solved

[0008] However, the two-layer interface is a complex dispersion system with high interfacial free energy, which leads to the thermodynamic instability of the double emulsion, often delamination or sedimentation, flocculation, coalescence, deformation or phase transition

In the double emulsion process such as CN1318028C, surfactants are added to both the inner water phase and the outer water phase, which increases the instability of the interface, thus causing a large number of demulsification, which reduces the reproducibility of production. Different batches Substandard products have large differences in performance, which is not easy for industrial scale-up production

Images