A loratadine syrup and a method for preparing the same
By optimizing the preparation process of loratadine syrup and adding the chelating agent disodium edetate, the problems of insufficient water solubility and stability of loratadine have been solved, resulting in a highly efficient and long-term stable liquid formulation suitable for industrial production.
Patent Information
- Application Number
- CN202610371159.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-03-25
- Publication Date
- 2026-06-02
AI Technical Summary
Loratadine suffers from poor water solubility and insufficient stability, which makes it difficult to dissolve in solid dosage forms, affecting its efficacy, and also poses a risk of precipitation in liquid dosage forms.
By optimizing the particle size of the active pharmaceutical ingredient and the preparation process, and by adding solubilizer 1,2-propanediol, thickener glycerol, sweetener sucrose, pH adjuster citric acid, antibacterial agent sodium benzoate and chelating agent disodium edetate, the particle size D90 was controlled to be ≤20μm, and the dissolution and mixing sequence was optimized, a loratadine syrup with good stability was prepared.
It significantly reduces the dissolution time of the active pharmaceutical ingredient, improves the stability of loratadine syrup, and reduces the generation of impurities after long-term storage, making it suitable for large-scale industrial production.
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Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a loratadine syrup and a preparation method thereof. BACKGROUND
[0002] Loratadine is a second-generation antihistamine drug, which is often used for treating allergic symptoms. Compared with the first-generation antihistamine drug, loratadine has the characteristic of no drowsiness. Loratadine is used for allergic rhinitis, acute or chronic urticaria, allergic conjunctivitis, hay fever and other allergic skin diseases.
[0003] The dosage forms of loratadine selected in clinical practice include tablets, syrups and granules. Loratadine has poor water solubility, so the drug is difficult to dissolve in solid preparations such as tablets, so that the drug cannot achieve the desired therapeutic effect. Liquid preparations such as syrups and oral solutions have high bioavailability, and are particularly suitable for children and patients with difficulty in swallowing.
[0004] Loratadine is easily soluble in methanol, ethanol or acetone, slightly soluble in 0.1 mol / L hydrochloric acid solution, and almost insoluble in water, which leads to the risk of precipitation during the storage of the syrup with water as the main solvent. Therefore, the dissolution and stability of the raw materials are the key points of the product and the common problems faced. SUMMARY
[0005] Based on the above reasons, the applicant has obtained a loratadine syrup with good solubility and excellent stability through many creative experiments. The loratadine syrup provided by the application optimizes the particle size requirement of the raw material, further optimizes the dissolution and mixing order of each raw material and auxiliary material in the preparation process of the syrup, and greatly reduces the dissolution time of the raw material. The loratadine syrup provided by the application adds the chelating agent disodium edetate, and the generated impurities are significantly lower than those of the original preparation after long-term storage, so that the loratadine syrup has good stability. The problems of the existing loratadine dissolution and insufficient stability are solved.
[0006] The application is realized through the following technical scheme:
[0007] A loratadine syrup, which contains: loratadine, a solubilizing agent, a thickening agent, a sweetening agent, a pH regulator, a flavoring agent, a bacteriostatic agent and a chelating agent.
[0008] The loratadine syrup, wherein the particle size D90 of the loratadine is greater than 0 and less than or equal to 20 mu m.
[0009] The loratadine syrup, wherein the solubilizing agent is 1,2-propanediol, the thickening agent is glycerol, the sweetening agent is sucrose, the flavoring agent is white peach essence, the pH regulator is citric acid, the bacteriostatic agent is sodium benzoate, and the chelating agent is disodium edetate.
[0010] The loratadine syrup comprises 1 part by weight of loratadine, 90-110 parts by weight of 1,2-propanediol as a solubilizer, 90-110 parts by weight of glycerin as a thickener, 550-650 parts by weight of sucrose as a sweetener, 2-3 parts by weight of white peach flavoring as a flavoring agent, 9-10 parts by weight of citric acid as a pH adjuster, 0.5-1.5 parts by weight of sodium benzoate as an antibacterial agent, and 0.20-0.30 parts by weight of disodium edetate as a chelating agent.
[0011] The loratadine syrup comprises 1 part by weight of loratadine, 100 parts by weight of 1,2-propanediol as a solubilizer, 100 parts by weight of glycerin as a thickener, 600 parts by weight of sucrose as a sweetener, 2.5 parts by weight of white peach flavoring as a flavoring agent, 9.6 parts by weight of citric acid as a pH adjuster, 1 part by weight of sodium benzoate as an antibacterial agent, and 0.25 parts by weight of disodium edetate as a chelating agent.
[0012] The loratadine syrup is characterized in that the preparation method of the syrup is as follows:
[0013] (1) The active ingredient loratadine was micronized, and the particle size limit D90 was controlled to be ≤20μm;
[0014] (2) Add loratadine with qualified particle size to propylene glycol, stir for 30-60 minutes until completely dissolved, then add the flavoring agent white peach flavoring, stir until evenly mixed, and prepare solution I;
[0015] (3) Boil purified water and cool it down to 80°C. Add sucrose and dissolve it for 30 minutes. Then add sodium benzoate, glycerol, disodium edetate and citric acid in sequence. Stir until completely dissolved and then cool down to prepare solution II. The pH value of solution II is controlled at 2.4~2.8.
[0016] (4) Transfer solution I to solution II, mix well, make up to volume, filter, and fill to obtain loratadine syrup.
[0017] The positive and progressive effects of this invention are as follows:
[0018] This invention optimizes the particle size requirements of the active pharmaceutical ingredient (API) and further optimizes the dissolution and mixing sequence of various raw materials and excipients during syrup preparation, significantly reducing the dissolution time of the API. The loratadine syrup provided by this invention, with the addition of the chelating agent disodium edetate, exhibits significantly lower levels of impurities after long-term storage compared to the original formulation, demonstrating excellent stability. This solves the existing problems of loratadine dissolution and insufficient stability.
[0019] The preparation process of this invention is simple, involves few steps, and is controllable, making it suitable for large-scale industrial production and possessing high industrial application value. Detailed Implementation
[0020] To make the technical means, creative features, objectives, and effects of this invention easier to understand, the invention is further illustrated below with reference to specific embodiments. However, the following embodiments are merely preferred embodiments of this invention and not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments described herein without creative effort are all within the protection scope of this invention.
[0021] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the materials and reagents used in the following examples are commercially available unless otherwise specified.
[0022] The research process of this application is as follows:
[0023] Example 1
[0024] Flavoring agent type screening
[0025] Adding flavoring agents to syrups can enhance the acceptability of a product's taste. We screen flavorings from different manufacturers and of different types.
[0026] Table 1. Screening of Flavoring Agents
[0027]
[0028] Preparation process: See Example 3.
[0029] Test results: As can be seen from the above data, all the formulation samples were clear and transparent. However, based on the results of aroma, taste, and aftertaste, white peach flavoring No. 98AF6436 was the best.
[0030] Example 2
[0031] Investigation of loratadine syrup chelating agents
[0032] Based on the properties of the active pharmaceutical ingredient, loratadine exhibits poor stability under oxidative conditions. Therefore, adding a chelating agent can increase the product's stability.
[0033] Table 2 Screening of chelating agents
[0034]
[0035] Preparation process: Same as in Example 3.
[0036] Table 3. Experimental Results
[0037]
[0038] Experimental Conclusion: The above experimental results show that, without disodium edetate (Formula 4), the levels of impurities 4-HML, 2-HML, and total impurities increased significantly under high-temperature conditions, while the addition of disodium edetate significantly improved these levels. Furthermore, the properties, clarity, color, pH value, content, and related substances of samples prepared with different amounts of disodium edetate showed no significant changes. Under high-temperature conditions, the levels of impurities 4-HML, 2-HML, and total impurities increased slightly with time, but all remained within acceptable limits and showed no significant changes.
[0039] Example 3
[0040] A loratadine syrup and its preparation method
[0041] The loratadine syrup formulation is as follows.
[0042] Table 4
[0043]
[0044] Preparation process:
[0045] (1) The active ingredient loratadine was micronized and the particle size limit D90 was controlled to be ≤20μm.
[0046] (2) Add loratadine with qualified particle size to propylene glycol and stir for 30-60 minutes until completely dissolved. Then add the flavoring agent white peach flavoring and stir until evenly mixed to prepare solution I.
[0047] (3) After boiling the purified water, cool it to 80°C, add sucrose and dissolve it for 30 minutes. Then add sodium benzoate, glycerol, disodium edetate, and citric acid in sequence, stirring until completely dissolved, and then cool down. Prepare solution II. The pH value of solution II is controlled at 2.4~2.8.
[0048] (4) Transfer solution I to solution II, mix well, make up to volume, filter, and fill to obtain loratadine syrup.
[0049] (5.) The dissolution times of the active pharmaceutical ingredient in the three batches of samples prepared in Example 1 are shown in the table below:
[0050] Table 5
[0051]
[0052] (6) The sample from Example 1 was compared with the commercially available formulation Claritin. @ Placement acceleration and long-term stability were assessed. The results are shown in the table below:
[0053] Table 6
[0054]
[0055] Table 7
[0056]
[0057]
[0058] Obviously, the above embodiments are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Their purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly, and they should not be used to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.
Claims
1. A loratadine syrup, characterized in that... This syrup contains: loratadine, solubilizer, thickener, sweetener, pH adjuster, flavoring agent, antibacterial agent, and chelating agent.
2. The loratadine syrup according to claim 1, wherein the loratadine particle size D 90 Greater than zero and less than or equal to 20 μm.
3. The loratadine syrup according to claim 1, wherein the solubilizer is 1,2-propanediol, the thickener is glycerol, the sweetener is sucrose, the flavoring agent is white peach flavoring, the pH adjuster is citric acid, the antibacterial agent is sodium benzoate, and the chelating agent is disodium edetate.
4. A loratadine syrup according to any one of claims 1-3, wherein loratadine is 1 part by weight, 1,2-propanediol is 90-110 parts by weight as a solubilizer, glycerin is 90-110 parts by weight as a thickener, sucrose is 550-650 parts by weight as a sweetener, white peach flavoring is 2-3 parts by weight as a flavoring agent, citric acid is 9-10 parts by weight as a pH adjuster, sodium benzoate is 0.5-1.5 parts by weight as an antibacterial agent, and disodium edetate is 0.20-0.30 parts by weight as a chelating agent.
5. A loratadine syrup according to any one of claims 1-3, wherein loratadine is 1 part by weight, 100 parts by weight of 1,2-propanediol is a solubilizer, 100 parts by weight of glycerol is a thickener, 600 parts by weight of sucrose is a sweetener, 2.5 parts by weight of white peach flavoring is a flavoring agent, 9.6 parts by weight of citric acid is a pH adjuster, 1 part by weight of sodium benzoate is an antibacterial agent, and 0.25 parts by weight of disodium edetate is a chelating agent.
6. A loratadine syrup according to claim 4 or 5, characterized in that, The preparation method of this syrup is as follows: (1) The active ingredient loratadine was micronized, and the particle size limit D90 was controlled to be ≤20μm; (2) Add loratadine with qualified particle size to propylene glycol, stir for 30-60 minutes until completely dissolved, then add the flavoring agent white peach flavoring, stir until evenly mixed, and prepare solution I; (3) Boil purified water and cool it down to 80°C. Add sucrose and dissolve it for 30 minutes. Then add sodium benzoate, glycerol, disodium edetate and citric acid in sequence. Stir until completely dissolved and then cool down to prepare solution II. The pH value of solution II is controlled at 2.4~2.
8. (4) Transfer solution I to solution II, mix well, make up to volume, filter, and fill to obtain loratadine syrup.