Emolol hydrochloride injection and preparation method thereof

Abstract

The invention provides an esmolol hydrochloride injection and a preparation method thereof. According to the esmolol hydrochloride injection, the pH value is adjusted to 4.5-5.0, and the increase of the impurity I and the total impurity is obviously reduced, so that the product stability is obviously improved.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an esmolol hydrochloride injection and a preparation method thereof. Background Art

[0002] Esmolol hydrochloride, a second-generation beta-adrenergic receptor blocker, was first approved in the United States in 1986. It is a receptor blocker with strong cardiac selectivity, rapid onset, and extremely short duration of action.

[0003] Esmolol hydrochloride is an ultra-short-acting selective β1-receptor blocker that inhibits β1-receptors mainly by competing for catecholamine binding sites in the myocardium. It has the effects of slowing down resting and exercise heart rate, lowering blood pressure, and reducing myocardial oxygen consumption.

[0004] It is mainly used to control the ventricular rate of supraventricular tachycardia, including atrial fibrillation, atrial flutter and non-compensated sinus tachycardia; and to control perioperative tachycardia and hypertension.

[0005] According to the current literature on the formulation process of esmolol hydrochloride injection, it is necessary to add an appropriate amount of antioxidant to enhance the stability of the preparation, and to add activated carbon filtration and other processes. The production steps are complicated and not conducive to industrial production. Summary of the Invention

[0006] The technical problem solved by the present invention is to provide an esmolol hydrochloride injection and a preparation process thereof, thereby improving the stability of the esmolol hydrochloride injection.

[0007] In order to achieve the above objectives, in a first aspect, the present invention provides an esmolol hydrochloride injection, wherein the pH value of the esmolol hydrochloride injection is 4.5-5.0.

[0008] Specifically, the raw materials and auxiliary materials of the esmolol hydrochloride injection include esmolol hydrochloride, sodium chloride (for injection), sodium acetate trihydrate, glacial acetic acid, sodium hydroxide, hydrochloric acid and water for injection.

[0009] Specifically, in the esmolol hydrochloride injection, the sodium acetate trihydrate and glacial acetic acid are used in combination as a buffer system of the pharmaceutical preparation.

[0010] Specifically, in the esmolol hydrochloride injection, the pH regulator is hydrochloric acid or sodium hydroxide solution.

[0011] In a second aspect, the present invention provides an esmolol hydrochloride injection, characterized in that it includes the steps of weighing, preparing, filtering, filling, sterilizing, and packaging.

[0012] Specifically, the preparation process includes adding the pH adjuster to adjust the pH value of the liquid to 4.5-5.0.

[0013] Specifically, in the potting process, the potting is performed by nitrogen filling until the residual oxygen content in the headspace is less than 3.0%.

[0014] Specifically, in the sterilization process, the sterilization temperature is 121° C. and the sterilization time is 12 minutes.

[0015] Compared with the prior art, the advantages of the present invention are as follows.

[0016] 1. The present invention controls the pH value of the liquid between 4.5 and 5.0, which is beneficial to reducing the growth rate of impurity I and total impurities during the stability period.

[0017] 2. The preparation method of esmolol hydrochloride injection provided by the present invention performs nitrogen filling before and after encapsulation to control the headspace residual oxygen to less than 3.0%, which is beneficial to reducing the growth rate of impurity I and total impurities during the stability period.

[0018] The esmolol hydrochloride injection prepared by the above technology has a significantly reduced growth trend of impurity I and total impurities during the stability process. DETAILED DESCRIPTION

[0019] In the following examples, unless otherwise specified, the test machines and instruments used are reagents and instruments commonly used in the field, and the methods used are conventional methods in the field. Those skilled in the art can know how to specifically implement the methods and achieve corresponding results based on the contents of the examples. Example

[0020] An esmolol hydrochloride injection, the prescription is as follows: composition Dosage Prescription composition analysis Esmolol hydrochloride 105mg Active ingredient Sodium chloride (for injection) 59mg Osmotic pressure regulators Sodium acetate trihydrate 28mg buffer glacial acetic acid 5.46mg buffer hydrochloric acid appropriate amount pH adjusters Sodium hydroxide appropriate amount pH adjusters Water for injection Set the volume solvent .

[0021] The preparation method of the esmolol hydrochloride injection comprises the following steps.

[0022] ① Weighing: Weigh the batch prescription amount of esmolol hydrochloride and excipients and set aside.

[0023] ② Preparation of liquid: Add 80% of the prescribed amount of water for injection, cool to no more than 30°C, stir and add the prescribed amount of sodium acetate trihydrate and glacial acetic acid, add sodium chloride (for injection) after dissolution, stir for 10 minutes until completely dissolved; add the prescribed amount of esmolol hydrochloride, measure the pH value after complete dissolution, and control the pH value to 4.5-5.0. If the pH is out of the range, use 1 mol / L sodium hydroxide or hydrochloric acid solution to adjust the pH to within the range, stir until completely dissolved, and add water for injection to the full amount.

[0024] ③Filtration: The liquid medicine is pressurized with compressed air and filtered through a 0.45μm primary filter; two 0.22μm sterilization filters are then passed to the filling buffer tank.

[0025] ④Filling: Use an ampoule filling machine for filling, control the filling volume range at 10.10~10.50ml, adjust the filling speed to 400 bottles / min, fill with nitrogen, and keep the residual oxygen level less than 3.0%.

[0026] ⑤Sterilization: The sterilization parameters are 121℃ for 12 minutes.

[0027] ⑥ Leak detection and packaging.

[0028] An esmolol hydrochloride injection, the prescription is as follows: composition Dosage Prescription composition analysis Esmolol hydrochloride 105mg Active ingredient Sodium chloride (for injection) 59mg Osmotic pressure regulators Sodium acetate trihydrate 28mg buffer glacial acetic acid 5.46mg buffer hydrochloric acid appropriate amount pH adjusters Sodium hydroxide appropriate amount pH adjusters Water for injection Set the volume solvent .

[0029] The preparation method of the esmolol hydrochloride injection comprises the following steps.

[0030] ① Weighing: Weigh the batch prescription amount of esmolol hydrochloride and excipients and set aside.

[0031] ② Preparation of liquid: Add 80% of the prescribed amount of water for injection, cool to no more than 30°C, stir and add the prescribed amount of sodium acetate trihydrate and glacial acetic acid, add sodium chloride (for injection) after dissolution, stir for 10 minutes until completely dissolved; add the prescribed amount of esmolol hydrochloride, measure the pH value after complete dissolution, and control the pH value to 4.0-4.5. If the pH is out of the range, use 1 mol / L sodium hydroxide or hydrochloric acid solution to adjust the pH to within the range, stir until completely dissolved, and add water for injection to the full amount.

[0032] ③Filtration: The liquid medicine is pressurized with compressed air and filtered through a 0.45μm primary filter; two 0.22μm sterilization filters are then passed to the filling buffer tank.

[0033] ④Filling: Use an ampoule filling machine for filling, control the filling volume range at 10.10~10.50ml, adjust the filling speed to 400 bottles / min, fill with nitrogen, and keep the residual oxygen level less than 3.0%.

[0034] ⑤Sterilization: The sterilization parameters are 121℃ for 12 minutes.

[0035] ⑥ Leak detection and packaging.

[0036] An esmolol hydrochloride injection, the prescription is as follows: composition Dosage Prescription composition analysis Esmolol hydrochloride 105mg Active ingredient Sodium chloride (for injection) 59mg Osmotic pressure regulators Sodium acetate trihydrate 28mg buffer glacial acetic acid 5.46mg buffer hydrochloric acid appropriate amount pH adjusters Sodium hydroxide appropriate amount pH adjusters Water for injection Set the volume solvent .

[0037] The preparation method of the esmolol hydrochloride injection comprises the following steps.

[0038] ① Weighing: Weigh the batch prescription amount of esmolol hydrochloride and excipients and set aside.

[0039] ② Preparation of liquid: Add 80% of the prescribed amount of water for injection, cool to no more than 30°C, stir and add the prescribed amount of sodium acetate trihydrate and glacial acetic acid, add sodium chloride (for injection) after dissolution, stir for 10 minutes until completely dissolved; add the prescribed amount of esmolol hydrochloride, measure the pH value after complete dissolution, and control the pH value to 5.0-5.5. If the pH is out of the range, use 1 mol / L sodium hydroxide or hydrochloric acid solution to adjust the pH to within the range, stir until completely dissolved, and add water for injection to the full amount.

[0040] ③Filtration: The liquid medicine is pressurized with compressed air and filtered through a 0.45μm primary filter; two 0.22μm sterilization filters are then passed to the filling buffer tank.

[0041] ④Filling: Use an ampoule filling machine for filling, control the filling volume range at 10.10~10.50ml, adjust the filling speed to 400 bottles / min, fill with nitrogen, and keep the residual oxygen level less than 3.0%.

[0042] ⑤Sterilization: The sterilization parameters are 121℃ for 12 minutes.

[0043] ⑥ Leak detection and packaging.

[0044] An esmolol hydrochloride injection is provided, which differs from Example 1 in that no nitrogen filling operation is performed during the filling process.

Claims

1. An esmolol hydrochloride injection, characterized in that: Its raw and auxiliary materials include esmolol hydrochloride, sodium chloride (for injection), sodium acetate trihydrate, glacial acetic acid, pH regulator and water for injection.

2. According to claim 1, it is characterized in that The pH regulator is hydrochloric acid or sodium hydroxide.

3. According to claim 2, it is characterized in that The pH value of the drug solution is adjusted to 4.5-5.0 using the pH regulator.

4. The esmolol hydrochloride injection according to claim 1, characterized in that The production steps include weighing, preparation, filtration, filling, sterilization and packaging.

5. According to claim 4, the esmolol hydrochloride injection is characterized in that, In the potting process, the potting is performed by nitrogen filling until the residual oxygen content in the headspace is less than 3.0%.