Method for controlling pH value of metoclopramide hydrochloride injection

Abstract

The invention discloses a method for controlling the pH value of metoclopramide hydrochloride injection, which comprises the following steps: S1, putting an ampoule into an ultrasonic cleaning machine, and carrying out primary cleaning by using deionized water to remove dust and greasy dirt on the surface; s2, immersing the cleaned ampoule in a treatment solution for a period of time, and repeatedly washing with deionized water until the pH value is close to neutral; s3, the rinsed ampoule is put into a drying oven, the temperature is set to be 100-120 DEG C, and drying is conducted for 1-2 hours; s4, liquid medicine is prepared, and the liquid medicine is packaged in the ampoule dried in S3, according to the method for controlling the pH value of the metoclopramide hydrochloride injection, by using the ampoule bottle subjected to acidizing treatment, the change of the pH value before and after sterilization and under the high-temperature acceleration condition is remarkably reduced, the stability and the curative effect of the medicine are ensured, and the method is suitable for large-scale popularization and application. The metoclopramide hydrochloride injection is ensured to keep high stability and safety in the production and storage processes, and the validity period of the medicine is prolonged.

Description

Technical Field

[0001] The invention relates to the technical field of controlling the pH value of metoclopramide hydrochloride injection, and in particular to a method for controlling the pH value of metoclopramide hydrochloride injection. Background Art

[0002] The pH value of metoclopramide hydrochloride injection is unstable during the preparation process, which may affect the stability and efficacy of the drug. In particular, the pH value changes more significantly before and after sterilization and under high temperature accelerated conditions.

[0003] When using ordinary ampoules, the pH value changes greatly before and after sterilization. Using pH regulators to control the pH value of the solution will introduce additional impurities, affecting the safety and stability of the drug. By optimizing the preparation process, such as temperature, pressure and other parameters, the pH value change can be controlled, but the effect is limited. To this end, we propose a method for controlling the pH value of metoclopramide hydrochloride injection. Summary of the invention

[0004] The object of the present invention is to provide a method for controlling the pH value of metoclopramide hydrochloride injection to solve the problems raised in the above background technology.

[0005] To achieve the above object, the present invention provides the following technical solution: a method for controlling the pH value of metoclopramide hydrochloride injection, characterized in that it comprises the following steps:

[0006] S1. Place the ampoule in an ultrasonic cleaning machine and use deionized water for preliminary cleaning to remove dust and oil on the surface;

[0007] S2, immersing the cleaned ampoule in the treatment solution, immersing for a period of time, and then repeatedly rinsing with deionized water until the pH value is close to neutral;

[0008] S3, placing the rinsed ampoule in an oven, setting the temperature to 100-120°C, and drying for 1-2 hours;

[0009] S4. Prepare a drug solution and seal the drug solution in the ampoule dried in S3.

[0010] Preferably, the treatment solution is one of a dilute hydrochloric acid solution and a nitric acid solution, with a concentration of 1%-5%, and the treatment time is 10-30 minutes.

[0011] Preferably, the treatment solution is one of a sodium hydroxide solution and a potassium hydroxide solution, with a concentration of 1%-5%, and the treatment time is 10-30 minutes.

[0012] Preferably, the treatment solution is a solution containing a coating material, and the treatment time is 10-60 min. In S2, the coated ampoule is placed in an oven, the temperature is set to 100-150° C., and cured for 1-2 hours, and the cured ampoule is naturally cooled to room temperature.

[0013] Preferably, the treatment solution is one of a silane solution and a PTFE solution.

[0014] Preferably, the preparation method of the S4 Chinese medicine solution is: pre-add 90% water into a container, the preparation temperature is about 30° C., and nitrogen is filled for 20 minutes; first add the prescribed amount of metoclopramide hydrochloride and stir to dissolve, then add the prescribed amount of sodium chloride and stir until dissolved, and fix the volume.

[0015] Preferably, in S4, 0.45 μm and 0.22 μm polyethersulfone filter membranes are used for filtration and then packaging is performed.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] By using acidified ampoules, the change in pH value before and after sterilization and under high-temperature accelerated conditions can be significantly reduced, ensuring the stability and efficacy of the drug, ensuring that metoclopramide hydrochloride injection maintains high stability and safety during production and storage, and extending the shelf life of the drug. DETAILED DESCRIPTION

[0018] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0019] The present invention provides a technical solution: a method for controlling the pH value of metoclopramide hydrochloride injection, characterized in that it comprises the following steps:

[0020] S1. Place the ampoule in an ultrasonic cleaning machine and use deionized water for preliminary cleaning to remove dust and oil on the surface;

[0021] S2, immersing the cleaned ampoule in the treatment solution, immersing for a period of time, and then repeatedly rinsing with deionized water until the pH value is close to neutral;

[0022] S3, placing the rinsed ampoule in an oven, setting the temperature to 100-120°C, and drying for 1-2 hours;

[0023] S4. Prepare a drug solution and seal the drug solution in the ampoule dried in S3.

[0024] As a preferred embodiment, the treatment solution is one of a dilute hydrochloric acid solution and a nitric acid solution, with a concentration of 1%-5%, and the treatment time is 10-30 minutes.

[0025] As a preferred embodiment, the treatment solution is one of a sodium hydroxide solution and a potassium hydroxide solution, with a concentration of 1%-5%, and the treatment time is 10-30 minutes.

[0026] As a preferred embodiment, the treatment solution is a solution containing a coating material, the treatment time is 10-60 minutes, and in S2, the coated ampoule is placed in an oven, the temperature is set to 100-150°C, and cured for 1-2 hours, and the cured ampoule is naturally cooled to room temperature.

[0027] As a preferred embodiment, the treatment solution is one of a silane solution and a PTFE solution.

[0028] As a preferred embodiment, the preparation method of the S4 Chinese medicine solution is: pre-add 90% water into a container, the preparation temperature is about 30°C, and nitrogen is filled for 20 minutes; first add the prescribed amount of metoclopramide hydrochloride and stir to dissolve, then add the prescribed amount of sodium chloride and stir until dissolved, and fix the volume.

[0029] As a preferred embodiment, in S4, 0.45 μm and 0.22 μm polyethersulfone filter membranes are used for filtration and then packaging is performed.

[0030] The test conditions were as follows: high temperature 60℃ (0 day, 10 days, 30 days), light illumination 4500±500lx, near-ultraviolet light 120μw / cm2 (0 day, 5 days, 10 days), and the effects of different ampoule treatment methods on the related substances, content and pH value of the drug solution were compared.

[0031] Inner packaging material inspection results

[0032]

[0033] in conclusion:

[0034] (1) This product is unstable under light conditions, and the storage conditions of this product have been clearly stated that it should be stored away from light. After 10 days of light exposure, the relevant substances of each sample were degraded to varying degrees. The degradation range of the ampoules treated with alkalization was the largest, followed by the coated and untreated ampoules, and the degradation range of the ampoules treated with acidification was the smallest; the pH values ​​all showed a downward trend, with the pH of the ampoules treated with alkalization decreasing the most (about 1.1), and the pH of the ampoules treated with acidification decreasing the least (about 0.3).

[0035] (2) Under high temperature conditions, the degradation degree of related substances in each sample was similar, but the pH growth trend was quite different. After 30 days of high temperature, the pH of the acidified ampoule increased by only about 0.3; the pH of the other three ampoules increased by 0.8 to 1.1, which exceeded the limit.

[0036] (3) Before and after sterilization, the pH growth trends of the samples were also quite different. The pH of the acidified ampoule only increased by about 0.1; the pH of the other three ampoules increased by about 0.7 to 0.8.

[0037] Comprehensive analysis: The pH value of the acidified ampoules changes minimally before and after sterilization and under high-temperature accelerated conditions, which is beneficial to the quality control of pH in production and the stability of pH during the shelf life. Therefore, acidified ampoules are selected as the inner packaging material.

[0038] Metoclopramide hydrochloride injection pH results

[0039]

[0040] in conclusion:

[0041] Ordinary ampoule: Under light conditions, the pH shows a downward trend; under high temperature conditions, the pH tends to increase, and the increase at 60℃ is significantly higher than that at 40℃.

[0042] Acidified ampoule: Under light conditions, the pH remains basically unchanged; under high temperature conditions, the pH remains basically unchanged.

[0043] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0044] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for controlling the pH value of metoclopramide hydrochloride injection, characterized in that: The following steps are involved: S1. Place the ampoule in an ultrasonic cleaning machine and use deionized water for preliminary cleaning to remove dust and oil on the surface; S2, immersing the cleaned ampoule in the treatment solution, immersing for a period of time, and then repeatedly rinsing with deionized water until the pH value is close to neutral; S3, placing the rinsed ampoule in an oven, setting the temperature to 100-120°C, and drying for 1-2 hours; S4. Prepare a drug solution and seal the drug solution in the ampoule dried in S3.

2. A method for controlling the pH value of metoclopramide hydrochloride injection according to claim 1, characterized in that: The treatment solution is one of a dilute hydrochloric acid solution and a nitric acid solution, with a concentration of 1%-5%, and the treatment time is 10-30 minutes.

3. A method for controlling the pH value of metoclopramide hydrochloride injection according to claim 1, characterized in that: The treatment solution is one of a sodium hydroxide solution and a potassium hydroxide solution, with a concentration of 1%-5%, and a treatment time of 10-30 minutes.

4. A method for controlling the pH value of metoclopramide hydrochloride injection according to claim 1, characterized in that: The treatment solution is a solution containing a coating material, and the treatment time is 10-60 minutes. In S2, the coated ampoule is placed in an oven, the temperature is set to 100-150° C., and cured for 1-2 hours, and the cured ampoule is naturally cooled to room temperature.

5. A method for controlling the pH value of metoclopramide hydrochloride injection according to claim 4, characterized in that: The treatment solution is one of a silane solution and a PTFE solution.

6. A method for controlling the pH value of metoclopramide hydrochloride injection according to claim 1, characterized in that: The preparation method of the S4 Chinese medicine solution is as follows: 90% water is pre-added into a container, the preparation temperature is about 30° C., and nitrogen is filled for 20 minutes; firstly, a prescribed amount of metoclopramide hydrochloride is added and stirred to dissolve, and then a prescribed amount of sodium chloride is added and stirred until dissolved, and the volume is fixed.

7. A method for controlling the pH value of metoclopramide hydrochloride injection according to claim 1, characterized in that: In the S4, 0.45 μm and 0.22 μm polyethersulfone filter membranes are used for filtration and packaging.

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