Oral spray of escitalopram oxalate and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an escitalopram oxalate oral spray and a preparation method thereof, and the escitalopram oxalate oral spray comprises the following components in percentage by weight: 1-15% of escitalopram oxalate, 0.5-5% of a pH buffer agent, 5-20% of a cosolvent, 0.02-30% of a flavoring agent, 1-6% of a humectant, 0.01-3% of a bacteriostatic agent and the balance of a solvent. The escitalopram oxalate oral spray has the beneficial effects that the escitalopram oxalate oral spray is more easily atomized by a spray pump, and the particle size distribution of sprayed liquid drops is uniform; according to the escitalopram oxalate oral spray, the selected flavoring agent can well cover the bitterness of escitalopram oxalate, and the taste covering effect can be achieved without too high addition of the selected flavoring agent, so that the drug effect cannot be influenced; after the escitalopram oxalate oral spray is placed for six months, the content of main components is almost not reduced, so that the stability is high after the escitalopram oxalate oral spray is placed for a long time.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an escitalopram oxalate oral spray and a preparation method thereof. Background Art

[0002] Spray refers to a preparation that is filled with raw materials or suitable excipients in a special device, and when used, the contents are released in the form of mist by the pressure of a manual pump, high-pressure gas, ultrasonic vibration or other methods, and sprayed directly onto the cavity mucosa or skin. Sprays are divided into solution type, emulsion type or suspension type according to the composition of the contents. According to the route of administration, they can be divided into oral spray, inhalation spray, nasal spray and spray for skin, etc. According to whether the dosage is quantitative or not, sprays can also be divided into quantitative sprays and non-quantitative sprays.

[0003] Escitalopram oxalate has significant clinical effects on the treatment of depressive disorders, panic disorders, social anxiety disorders, and generalized anxiety disorders. According to the World Health Organization, depression is currently the fourth largest disease burden in the world and one of the main causes of functional disability in patients. About 1 / 7 of people will suffer from depression at a certain stage in their lives. Prevention and treatment of depression are urgent, but most patients are depressed and painful, and it is difficult to concentrate and think normally. They have resistance to taking medicine, which leads to worsening of the condition. At present, the domestic marketed dosage forms are tablets and oral solutions. For mental patients, especially the elderly and children, ordinary tablets have poor oral compliance and slow onset, and the oral solution dosage is large, which is inconvenient to use and carry. At the same time, escitalopram oxalate is made into an oral spray, which has the problem of bitter taste, and the content of escitalopram oxalate in the oral spray increases, and the stability requirement for long-term storage is higher. Therefore, how to develop an escitalopram oxalate oral spray that is easy to take at any time, has high oral compliance, good stability and fast onset has become a problem to be solved. Summary of the invention

[0004] The purpose of the present invention is to solve the above problem and provide an oral spray of escitalopram oxalate and a preparation method thereof.

[0005] The invention relates to an escitalopram oxalate oral spray, which comprises, by weight percentage, 1-15% of escitalopram oxalate, 0.5-5% of a pH buffer, 5-20% of a cosolvent, 0.02-30% of a flavoring agent, 1-6% of a moisturizer, 0.01-3% of an antibacterial agent and the remainder of a solvent.

[0006] Preferably, the pH value of the oral spray is 4.0-6.0.

[0007] Preferably, the co-solvent is one or more of 15-hydroxystearate polyethylene glycol and polysorbate 80.

[0008] Preferably, the pH regulator is one or more of citric acid, sodium citrate, sodium hydroxide, sodium acetate and acetic acid.

[0009] Preferably, the flavoring agent is one or more of malic acid, xylitol, sorbitol, mannitol, acesulfame potassium, sucralose and essence.

[0010] Preferably, the flavor is strawberry flavor or orange flavor.

[0011] Preferably, the preservative is one or more of methylparaben, ethylparaben, propylparaben, potassium sorbate, sodium benzoate and benzalkonium chloride.

[0012] Preferably, the humectant is glycerin.

[0013] Preferably, the solvent is purified water.

[0014] The present invention also relates to a method for preparing an escitalopram oxalate oral spray. The preparation method of the escitalopram oxalate oral spray comprises the following specific steps: (1) Liquid preparation: Add the solvent, co-solvent and moisturizer into the liquid preparation tank, stir and dissolve, and heat to 40-50° C., add escitalopram oxalate and stir and dissolve, add the flavoring agent and antibacterial agent and stir and dissolve; cool to 25° C., add the pH adjuster and adjust the pH value of the liquid to 4.0-6.0; (2) Filling: Pour the liquid medicine into the spray bottle and install a spray pump.

[0015] Compared with the prior art, the advantages and positive effects of the present invention are: Compared with the prior art, the oral spray of escitalopram oxalate and the preparation method thereof of the present invention are (1) The flavoring agent selected for the escitalopram oxalate oral spray can effectively mask the bitterness of escitalopram oxalate, and the selected flavoring agent does not need to be added too much to achieve the taste-masking effect, thereby not affecting the efficacy of the drug; (2) After the escitalopram oxalate oral spray is placed for six months, the content of the main component hardly decreases, thereby providing high stability for long-term placement; (3) A cosolvent is added to the oral spray of escitalopram oxalate to improve the solubility of each component in the drug solution, thereby making it easier to atomize through a spray pump, so that the droplet particle size distribution of the spray is uniform; (4) The escitalopram oxalate oral spray has a high content of the main ingredient, a small dosage, and is easy to take at any time, thereby increasing the patient's compliance with the medication. DETAILED DESCRIPTION

[0016] In order to more clearly understand the above-mentioned objects, features and advantages of the present invention, the present invention is further described below in conjunction with embodiments.

[0017] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways than those described herein. Therefore, the present invention is not limited to the specific embodiments of the following disclosure.

[0018] Example 1 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol and glycerin into a preparation tank, stir to dissolve and heat to 40°C, add escitalopram oxalate and stir to dissolve, add xylitol, flavor, malic acid, methylparaben and propylparaben and stir to dissolve; cool to 25°C, add citric acid and sodium citrate to adjust the pH value of the solution to 4.0.

[0019] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0020] Example 2 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol and glycerin into the preparation tank, stir to dissolve and heat to 50°C, add escitalopram oxalate and stir to dissolve, add xylitol, orange flavor, methylparaben and propylparaben and stir to dissolve; cool to 25°C, add citric acid and sodium citrate to adjust the pH value of the solution to 4.5.

[0021] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0022] Example 3 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol and glycerin into a preparation tank, stir to dissolve and raise the temperature to 40°C, add escitalopram oxalate and stir to dissolve, add xylitol, orange flavor, methylparaben and propylparaben and stir to dissolve; cool to 25°C, add citric acid and sodium citrate to adjust the pH value of the solution to 5.0.

[0023] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0024] Example 4 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol and glycerin into the preparation tank, stir to dissolve and heat to 45°C, add escitalopram oxalate and stir to dissolve, add xylitol, strawberry flavor, methylparaben and propylparaben and stir to dissolve; cool to 25°C, add citric acid and sodium citrate to adjust the pH value of the solution to 5.5.

[0025] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0026] Example 5 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol and glycerol into the preparation tank, stir to dissolve and heat to 45°C, add escitalopram oxalate and stir to dissolve, add sucralose, methylparaben and propylparaben and stir to dissolve; cool to 25°C, add citric acid and sodium citrate to adjust the pH value of the solution to 6.0.

[0027] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0028] Example 6 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol and glycerol into the preparation tank, stir to dissolve and heat to 50°C, add escitalopram oxalate and stir to dissolve, add sucralose, methylparaben and propylparaben and stir to dissolve; cool to 25°C, add citric acid and sodium hydroxide to adjust the pH value of the solution to 4.0.

[0029] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0030] Example 7 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol, polysorbate 80 and glycerol into a preparation tank, stir to dissolve and raise the temperature to 40°C, add escitalopram oxalate and stir to dissolve, add xylitol and benzalkonium chloride and stir to dissolve; cool to 25°C, add citric acid and sodium hydroxide to adjust the pH value of the solution to 5.0.

[0031] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0032] Example 8 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol, polysorbate 80 and glycerin into a preparation tank, stir to dissolve and heat to 40°C, add escitalopram oxalate and stir to dissolve, add xylitol, strawberry flavor, malic acid, methylparaben and propylparaben and stir to dissolve; cool to 25°C, add citric acid and sodium citrate to adjust the pH value of the solution to 4.5.

[0033] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0034] Comparative Example 1 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol and glycerol into the preparation tank, stir to dissolve and heat to 50°C, add escitalopram oxalate and stir to dissolve, add methylparaben and propylparaben and stir to dissolve; cool to 25°C, add citric acid and sodium citrate to adjust the pH value of the solution to 4.5.

[0035] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0036] Comparative Example 2 An oral spray of escitalopram oxalate, the formula of which is as follows: The preparation method is as follows: (1) Preparation: Add purified water, 15-hydroxystearate polyethylene glycol, polysorbate 80 and glycerol into the preparation tank, stir to dissolve and heat to 45°C, add escitalopram oxalate and stir to dissolve, add methylparaben and propylparaben and stir to dissolve; cool to 25°C, add citric acid and sodium citrate to adjust the pH value of the solution to 5.0.

[0037] (2) Filling: After pouring the liquid medicine into the spray bottle, install the spray pump.

[0038] Test example 1) Oral sensory evaluation was performed on the oral sprays of escitalopram oxalate of Examples 1-8 and Comparative Examples 1-2.

[0039] Table 1. Oral sensation evaluation results It can be concluded from Table 1 that the oral spray of escitalopram oxalate has a good taste, has no bitterness when taken, and can increase the compliance of patients with medication.

[0040] 2) The properties and related substances of the escitalopram oxalate oral sprays of Examples 1-8 were tested.

[0041] Table 2. Properties and related substances test results It can be concluded from Table 2 that in the oral spray of escitalopram oxalate, the maximum single impurity is less than 0.1%, the total impurities are less than 0.15%, and the content of the main component is greater than 99.0%.

[0042] 3) The escitalopram oxalate oral sprays of Examples 1-5 were subjected to a stability test at a temperature of 40°C ± 2°C and a relative humidity of 75% ± 5%.

[0043] Table 3. Results of stability test from 0 to 6 months It can be concluded from Table 3 that the oral spray of escitalopram oxalate is stable at a pH value of 4.0 to 6.0, and is more stable at a pH value of 4.5 to 5.5. After being placed for six months, the related substances and their contents are almost unchanged.

[0044] The above description is only a preferred embodiment of the present invention and does not limit the present invention in other forms. Any technician familiar with the profession may use the technical content disclosed above to change or modify it into an equivalent embodiment with equivalent changes for application in other fields. However, any simple modification or equivalent change made to the above embodiment based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. An oral spray of escitalopram oxalate, characterized in that: Calculated by weight percentage, it includes 1-15% of escitalopram oxalate, 0.5-5% of pH buffer, 5-20% of co-solvent, 0.02-30% of flavoring agent, 1-6% of moisturizer, 0.01-3% of antibacterial agent and the balance of solvent.

2. The oral spray of escitalopram oxalate according to claim 1, characterized in that The pH value of the oral spray is 4.0-6.

0.

3. The oral spray of escitalopram oxalate according to claim 2, characterized in that: The cosolvent is one or more of 15-hydroxystearate polyethylene glycol and polysorbate 80.

4. The oral spray of escitalopram oxalate according to claim 3, characterized in that: The pH regulator is one or more of citric acid, sodium citrate, sodium hydroxide, sodium acetate and acetic acid.

5. The oral spray of escitalopram oxalate according to claim 4, characterized in that: The flavoring agent is one or more of malic acid, xylitol, sorbitol, mannitol, acesulfame potassium, sucralose and essence.

6. The oral spray of escitalopram oxalate according to claim 5, characterized in that: The flavor is strawberry flavor or orange flavor.

7. The oral spray of escitalopram oxalate according to claim 6, characterized in that: The preservative is one or more of methylparaben, ethylparaben, propylparaben, potassium sorbate, sodium benzoate and benzalkonium chloride.

8. The oral spray of escitalopram oxalate according to claim 7, characterized in that: The humectant is glycerin.

9. The oral spray of escitalopram oxalate according to claim 8, characterized in that The solvent is purified water.

10. A method for preparing an oral spray of escitalopram oxalate, comprising preparing the oral spray of escitalopram oxalate according to claim 9, characterized in that: The specific steps are as follows: (1) Liquid preparation: Add the solvent, co-solvent and moisturizer into the liquid preparation tank, stir and dissolve, and heat to 40-50° C., add escitalopram oxalate and stir and dissolve, add the flavoring agent and antibacterial agent and stir and dissolve; cool to 25° C., add the pH adjuster and adjust the pH value of the liquid to 4.0-6.0; (2) Filling: Pour the liquid medicine into the spray bottle and install a spray pump.

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