Stable cetirizine hydrochloride drop and preparation method thereof

Abstract

The invention relates to the technical field of medicine preparation, and discloses a stable cetirizine hydrochloride drop and a preparation method thereof, the cetirizine hydrochloride drop comprises a cetirizine hydrochloride bulk drug, a solvent, a flavoring agent, a bacteriostatic agent, a pH regulator and other pharmaceutically common auxiliary materials; wherein the pH value of the cetirizine hydrochloride drop is regulated to 5.3 to 5.5 by the pH regulator; the pH regulator is sodium acetate and glacial acetic acid. The invention overcomes the defect of poor stability of cetirizine hydrochloride drops prepared in the prior art, provides a technical method for preparing the stable cetirizine hydrochloride drops, optimizes the pH value of the product, and realizes higher stability of the cetirizine hydrochloride drops.

Description

Technical Field

[0001] The invention relates to the technical field of medicine preparation, and in particular to a stable cetirizine hydrochloride drop and a preparation method thereof. Background Art

[0002] Cetirizine hydrochloride is a second-generation H1 antihistamine. As a new antihistamine, it is mainly used to relieve allergic symptoms of allergic diseases. It is clinically used to treat allergic rhinitis, urticaria, angioedema and other skin and mucous membrane allergic diseases. It has many advantages such as rapid oral absorption, high receptor selectivity, strong clinical efficacy, few side effects and good safety. It is the first choice drug for the treatment of allergic diseases.

[0003] Chinese patent CN100508981C discloses a method for preparing cetirizine hydrochloride drops and discloses the relevant formula of cetirizine hydrochloride drops. The cetirizine hydrochloride drops prepared by this method have poor stability, and the related substances (cetirizine glyceride, cetirizine propylene glycol ester 1, cetirizine propylene glycol ester 2, other single impurities and total impurities) increase rapidly.

[0004] According to research, the degradation impurities cetirizine glyceride, cetirizine propylene glycol ester 1, and cetirizine propylene glycol ester 2 are produced by the condensation of the active ingredient cetirizine hydrochloride with the excipients glycerol and propylene glycol (see below). The growth of such impurities is directly related to the pH value of the solution: the smaller the pH value, the faster the growth, and the larger the pH value, the slower the growth.

[0005] In addition, the prescription contains the antibacterial agents methylparaben and propylparaben, which degrade to produce parahydroxybenzoic acid (see below). The growth of this impurity is also directly related to the pH value of the solution: the smaller the pH value, the slower the growth, and the larger the pH value, the faster the growth.

[0006]

[0007] Therefore, the present application aims to develop a more stable cetirizine hydrochloride drops by controlling the pH value of the product to ensure that the product quality is stable, safe and controllable. Summary of the invention

[0008] Purpose of the invention: In view of the problems existing in the prior art, the present invention provides a stable cetirizine hydrochloride drops and a preparation method thereof, and achieves higher stability of the cetirizine hydrochloride drops by reasonably adjusting the formula components and controlling the pH value of the cetirizine hydrochloride drops.

[0009] Technical solution: The present invention provides a stable cetirizine hydrochloride drops, which contain cetirizine hydrochloride raw materials, solvents, flavoring agents, antibacterial agents, pH regulators and other commonly used pharmaceutical excipients; wherein the pH value of the cetirizine hydrochloride drops is adjusted to 5.3-5.5 by the pH regulator; the pH regulator is sodium acetate and glacial acetic acid.

[0010] Furthermore, the solvent is one or more of glycerol, propylene glycol or purified water.

[0011] Furthermore, the flavoring agent is sodium saccharin.

[0012] Furthermore, the antibacterial agent is methylparaben and propylparaben.

[0013] Furthermore, the mass percentage of the cetirizine hydrochloride raw material in the cetirizine hydrochloride drops is 0.87%-0.96%.

[0014] The present invention also provides a method for preparing the cetirizine hydrochloride drops as described in any one of the above items, the specific steps being as follows: S1. According to the prescription amount, weigh cetirizine hydrochloride API, solvent, flavoring agent, antibacterial agent and sodium acetate for use; the solvent is glycerol, propylene glycol and purified water; S2. At 40-45°C, mix glycerin and propylene glycol evenly, add antibacterial agent and flavoring agent, and stir to dissolve; S3. When the temperature of the mixed solution obtained in S2 drops to 25 ° C, add the cetirizine hydrochloride raw material and stir to dissolve; S4. Sodium acetate was added to the mixed solution obtained in S3, and the volume was adjusted with purified water, stirred to dissolve, and the pH value of the solution was adjusted to 5.3-5.5 using glacial acetic acid; S5. The mixed liquid obtained in S4 is filtered and filled in a dark-proof manner to obtain cetirizine hydrochloride drops.

[0015] Data Analysis: The applicant studied the stability of cetirizine hydrochloride drops at different pH values, and the research data are as follows: Table 1

[0016] The results showed that considering the growth trends of cetirizine glyceride, cetirizine propylene glycol ester 1, cetirizine propylene glycol ester 2 and p-hydroxybenzoic acid, the stability of cetirizine hydrochloride drops at pH 5.4±0.1 was better than that at pH 4.9±0.1 and pH 6.0±0.1.

[0017] Beneficial effects: Compared with the prior art, the present invention has the following specific beneficial effects: The present invention overcomes the disadvantage of poor stability of cetirizine hydrochloride drops prepared by the prior art, provides a technical method for preparing stable cetirizine hydrochloride drops, and achieves higher stability of cetirizine hydrochloride drops by rationally adjusting the formulation components, optimizing the product pH value, and controlling the pH value of the cetirizine hydrochloride drops to 5.3-5.5. The product quality prepared by the method provided by the present invention is stable, safe and controllable, and the stability is better than that of the original drug. DETAILED DESCRIPTION

[0018] The present invention is described in detail below in conjunction with the embodiments.

[0019] Implementation 1: The present embodiment provides a stable cetirizine hydrochloride drops, which are prepared from cetirizine hydrochloride raw materials, glycerol, propylene glycol, saccharin sodium, methylparaben, propylparaben, sodium acetate and purified water, and the pH value thereof is adjusted to 5.3-5.5 by glacial acetic acid. The specific prescription composition of the cetirizine hydrochloride drops is as follows: Table 2

[0020] Implementation 2: This embodiment provides a method for preparing a stable cetirizine hydrochloride drops, which is as follows: 1. Bottle washing Brown soda-lime glass molded medicine bottles are filled with circulating water, ultrasonically vibrated by a vertical ultrasonic cleaner, and dried by a turntable water vapor cleaning before being transferred to a tunnel-type sterilization dryer. Oral liquid bottles are dried in a tunnel-type sterilization dryer, with the sterilization heating temperature set, until there is no visible water in the oral liquid bottles.

[0021] 2. Weighing According to implementation mode 1, weigh the raw and auxiliary materials (except glacial acetic acid) in the prescribed amount and set aside.

[0022] 3. Liquid preparation 1) Add the prescribed amount of propylene glycol and glycerin into the preparation tank (set temperature 45°C) and stir the solution until it is mixed evenly.

[0023] 2) Add the prescribed amount of methylparaben, propylparaben and sodium saccharin into the preparation tank and stir to dissolve.

[0024] 3) Turn off the heating of the equipment, wait for the liquid to cool down to 25°C, add the prescribed amount of cetirizine hydrochloride, and stir to dissolve.

[0025] 4) Add the prescribed amount of sodium acetate, add purified water to make up to volume, stir to dissolve, and use glacial acetic acid to adjust its pH value to a range of 5.3-5.5.

[0026] 4. Filter Filter the prepared solution using a 0.45 μm polyethersulfone (PES) filter element.

[0027] 5. Potting The filtered solution is filled into brown soda-lime glass molded pharmaceutical bottles and then capped with dropper stoppers.

[0028] 6. Packaging

[0029] This comparative example provides a cetirizine hydrochloride drops (original drug), the specific prescription composition is as follows: Table 3

[0030] The newly purchased original drug and the preparation prepared according to Implementation Example 1 were placed at 60° C. for 30 days, and the impurity content was tested. The results are shown in Table 4.

[0031] Table 4

[0032] The results show that, except for p-hydroxybenzoic acid, the impurities of the original drug increase significantly faster than those of the preparation prepared in Implementation Example 1.

[0033] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent transformation or modification made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A stable cetirizine hydrochloride drops, characterized in that: The cetirizine hydrochloride drops contain cetirizine hydrochloride raw materials, solvents, flavoring agents, antibacterial agents, pH regulators and other commonly used pharmaceutical excipients; wherein the pH value of the cetirizine hydrochloride drops is adjusted to 5.3-5.5 by the pH regulator; the pH regulator is sodium acetate and glacial acetic acid.

2. The stable cetirizine hydrochloride drops according to claim 1, characterized in that: The solvent is one or more of glycerol, propylene glycol or purified water.

3. The stable cetirizine hydrochloride drops according to claim 1, characterized in that: The flavoring agent is saccharin sodium.

4. The stable cetirizine hydrochloride drops according to claim 1, characterized in that: The antibacterial agents are methylparaben and propylparaben.

5. The stable cetirizine hydrochloride drops according to claim 1, characterized in that: The mass percentage of the cetirizine hydrochloride raw material in the cetirizine hydrochloride drops is 0.87%-0.96%.

6. The method for preparing the cetirizine hydrochloride drops according to any one of claims 1 to 5, characterized in that: The specific steps are as follows: S1. According to the prescription amount, weigh cetirizine hydrochloride API, solvent, flavoring agent, antibacterial agent and sodium acetate for use; the solvent is glycerol, propylene glycol and purified water; S2. At 40-45°C, mix glycerin and propylene glycol evenly, add antibacterial agent and flavoring agent, and stir to dissolve; S3. When the temperature of the mixed solution obtained in S2 drops to 25 ° C, add the cetirizine hydrochloride raw material and stir to dissolve; S4. Sodium acetate was added to the mixed solution obtained in S3, and the volume was adjusted with purified water, stirred to dissolve, and the pH value of the solution was adjusted to 5.3-5.5 using glacial acetic acid; S5. The mixed liquid obtained in S4 is filtered and filled in a dark-proof manner to obtain cetirizine hydrochloride drops.

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