Freeze drying process applied to preparation of isiomerazole

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a freeze-drying process applied to preparation of isimerazole. Comprising the following steps: (1) adding bulk drugs at 25 DEG C or below in the process; (2) the pre-freezing temperature of a finished product is-35 DEG C, the sublimation temperature is 0 DEG C, the vacuum pressure is 0.5 + / -0.05 mbar, and the desorption drying temperature is 30 DEG C; and in the step (3), unknown impurities are less than 0.2% through detection.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to a freeze-drying process used in the preparation of esomeprazole. Background Art

[0002] Esomeprazole is the S-isomer of omeprazole. It reduces gastric acid secretion through specific proton pump inhibition. The R-isomer and S-isomer of omeprazole have similar pharmacodynamic properties. Esomeprazole is a weakly alkaline drug. It is concentrated and converted into an active form in the high acid environment of the acid secretory microtubules of parietal cells, thereby inhibiting the H+ / K+-ATPase (proton pump) in this area, and inhibiting both basal gastric acid secretion and gastric acid secretion after stimulation.

[0003] Freeze-drying technology refers to a technology that directly sublimates water from solid to gas in a vacuum environment below zero degrees, extracting the moisture in the product and thus completely preserving the activity of biological components.

[0004] Esomeprazole is a lyophilized powder for injection. The production process mainly includes drug solution preparation, sterilization filtration, and freeze drying. The key steps include the pH range of the drug solution, the temperature and light stability of the drug solution, filtration, freeze drying, etc.

[0005] Freeze drying is a critical process step and all activities that may affect the sterility of the product or material can be considered as an extension of the aseptic operation of the sterilized product or material. The design of the freeze drying equipment and its process should ensure that the sterility of the product or material is maintained during freeze drying by preventing microbial and particle contamination between the filling operation and the end of the freeze drying process. All control measures should be determined by the on-site contamination control strategy. Summary of the invention

[0006] The object of the present invention is to provide a freeze-drying process for the preparation of esomeprazole, which is conducive to large-scale mass production and optimizes the freeze-drying process of the preparation.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] A freeze-drying process for preparing esomeprazole comprises the following steps:

[0009] In step (1), the temperature is controlled below 25° C. during the process to add the raw material drug;

[0010] The pre-freezing temperature of the finished product in step (2) is -35°C, the sublimation temperature is 0°C, the vacuum pressure is 0.5±0.05mbar, and the analytical drying temperature is 30°C;

[0011] Step (3) is tested to make the unknown impurities less than 0.2%.

[0012] In the step (2), through the freeze-drying process optimization experiment, it is determined that the pre-freezing temperature of the product is -35°C, the sublimation temperature is 0°C, the vacuum pressure is 0.15±0.05mbar, and the analytical drying temperature is 30°C.

[0013] Compared with the prior art, the present invention has the following beneficial effects:

[0014] The present invention can reduce process costs and cycles, improve the understanding of the effects of prescriptions and processes on drug stability, determine key quality attributes, and obtain stable and good products with small intra-batch and inter-batch differences in net quantity. DETAILED DESCRIPTION

[0015] 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.

[0016] Example.

[0017] A freeze-drying process for preparing esomeprazole comprises the following steps:

[0018] In step (1), the temperature is controlled below 25° C. during the process to add the raw material drug;

[0019] The pre-freezing temperature of the finished product in step (2) is -35°C, the sublimation temperature is 0°C, the vacuum pressure is 0.5±0.05mbar, and the analytical drying temperature is 30°C;

[0020] Step (3) is tested to make the unknown impurities less than 0.2%.

[0021] In the step (2), through the freeze-drying process optimization experiment, it is determined that the pre-freezing temperature of the product is -35°C, the sublimation temperature is 0°C, the vacuum pressure is 0.15±0.05mbar, and the analytical drying temperature is 30°C.

[0022] This product is a sterile freeze-dried preparation. The metal ion chelating agent disodium edetate is added during the production process to inhibit the insoluble drug particles and effectively avoid adverse reactions.

[0023] The research and analysis of the preparation of the drug solution found that the lower the pH value, the more unstable the AS. Through screening experiments and PI-I value screening experiments, the pH value of the intermediate solution of this product was set between 11.0-11.5, and the pH value of the finished product was between 10.0-11.0.

[0024] The use of alkali-resistant polyol filter membrane can effectively avoid abnormal phenomena of sterile products and improve product quality; the filter membrane compatibility test results also show that it has good compatibility with this product.

Claims

1. A freeze-drying process for the preparation of esomeprazole, characterized in that The method comprises the following steps: step (1) adding the raw material drug at a temperature below 25° C. during the process; The pre-freezing temperature of the finished product in step (2) is -35°C, the sublimation temperature is 0°C, the vacuum pressure is 0.5±0.05mbar, and the analytical drying temperature is 30°C; Step (3) is tested to make the unknown impurities less than 0.2%.

2. The freeze-drying process for preparing esomeprazole according to claim 1, characterized in that In the step (2), through the freeze-drying process optimization experiment, it is determined that the pre-freezing temperature of the product is -35°C, the sublimation temperature is 0°C, the vacuum pressure is 0.15±0.05mbar, and the analytical drying temperature is 30°C.