Tiotropium solution for inhalation

Abstract

The invention provides a tiotropium solution for inhalation. The tiotropium solution comprises tiotropium salt, single water or a water / ethanol mixture, acetylcysteine and other optional pharmacologically acceptable auxiliary materials, wherein the tiotropium salt is used as an active substance, and the concentration of the tiotropium salt is 0.0005-5% by weight based on tiotropium; the single water or the water / ethanol mixture is used as a solvent of the active substance; and the acetylcysteine is used as a stabilizer. The tiotropium solution has the beneficial effects that in the research and development process of the tiotropium solution, the condition that the storage of the tiotropium solution is more stable by adding 0.15-0.5% of the acetylcysteine is accidentally found, related substances of the preparation are reduced, and the safety and effectiveness of the medicine are guaranteed.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, in particular to a tiotropium solution for inhalation. Background technique [0002] Tiotropium bromide is the first long-acting inhaled anticholinergic drug (LAMA) developed and marketed by Boehringer Ingelheim. The chemical name is (1R,2R,4S,5S,7S)-7-[2- Hydroxy-2,2-bis(2-thienyl)acetoxy]-9,9-dimethyl-3-epoxy-9-azation tricyclooctane[3.3.1.02.4]nonane bromide, It is a synthetic non-chiral quaternary ammonium compound. [0003] [0004] Tiotropium bromide is white or yellow-white powder, slightly soluble in water, soluble in methanol. Its efficacy in the treatment of COPD has been fully clinically confirmed, and domestic and foreign guidelines recommend it as the first-choice drug for COPD. At present, there are tiotropium bromide powder inhalation and tiotropium bromide spray on the market. [0005] Tiotropium bromide spray is suitable for the maintenance treatment of chronic o...

AI Technical Summary

Problems solved by technology

[0006] During the development of tiotropium bromide spray, it was found that the long-term stability of the original formulation was poor. In the long-term stability test, more impurities were degraded after more than 24 months; the main degraded impurities were impurity I and impurity II

It is found through experiments that the original formulation has a narrow tolerance to pH, and is stable in the range of pH 2.8 to 3.0. As the pH value increases, the stability of the formulation becomes worse, and related substances increase, which is mainly related to the physical and chemical properties of tiotropium bromide. Related to the nature, tiotropium bromide itself is more sensitive to the pH value, which puts forward higher requirements for research and development and production, so it is necessary to develop a stable solution suitable for industrialized production of tiotropium bromide

Images