Bromhexine hydrochloride oral liquid and preparation method thereof

Abstract

The invention discloses bromhexine hydrochloride oral liquid and a preparation method thereof.The oral liquid is prepared from, by 5 ml of solution, 8 mg to 12 mg of bromhexine hydrochloride, 45 mg to 55 mg of liquorice root extract, 130 mg to 150 mg of glycerinum, 0.2 mg to 0.5 mg of fruit essence, 0.3 mg to 0.5 mg of sodium chloride, 0.2 mg to 0.4 mg of pH regulator, 0.1 mg to 0.3 mg of disodium hydrogen phosphate and purified water. The relative humidity is 60% + / -10%, and the total impurity amount can still be ignored after the oral liquid is placed for 12 months, which indicates that the bromhexine hydrochloride oral liquid in the scheme has better long-term stability and can be stored for a long time. According to the scheme, the licorice extract is heated to enhance the cough relieving effect, relieve throat discomfort and improve the taste, the glycerol is added, the taste can be improved, the viscosity and lubricity of the liquid medicine can be improved, and meanwhile the fruit essence is added to improve the taste, increase the acceptability and cover the bitter taste of the medicine.

Description

Technical Field

[0001] The present invention relates to the field of bromhexine hydrochloride oral solution, and more specifically, to a bromhexine hydrochloride oral solution and a preparation method thereof. Background Art

[0002] Bromhexine is a mucolytic agent with significant expectorant effects. It promotes the secretion of respiratory mucus, improves the consistency of mucus, increases its fluidity, thereby making sputum easier to expel, reducing airway obstruction, and improving respiratory function. Bromhexine can also promote the excretion of sputum by stimulating the ciliary movement of the respiratory tract. Bromhexine hydrochloride oral solution is a commonly used drug for treating respiratory diseases, especially suitable for symptoms such as excessive phlegm and cough in the upper or lower respiratory tract caused by infection. It can effectively help dilute and expel sputum in the airway, relieve symptoms such as dyspnea and cough.

[0003] During the storage of bromhexine hydrochloride oral solution, with the passage of time, slow degradation will occur. Now, in order to improve the stability of bromhexine hydrochloride oral solution, stabilizers such as sugar alcohols are added to the formula. However, the above substances will bring inconvenience to the preparation process. And because the main component of bromhexine hydrochloride oral solution is bromhexine hydrochloride, its taste is generally bitter and astringent, with a poor taste when taken, making it difficult to take orally, especially for younger patients, it is even more difficult to take. Summary of the Invention

[0004] The purpose of the present invention is to provide a bromhexine hydrochloride oral solution and a preparation method thereof to solve the technical problems existing in the above background art.

[0005] The technical solution of the present invention provides a bromhexine hydrochloride oral solution. Calculated based on 5 ml of solution, it includes the following components: 8 - 12 mg of bromhexine hydrochloride, 45 - 55 mg of licorice extract, 130 - 150 mg of glycerol, 0.2 - 0.5 mg of fruit essence, 0.3 - 0.5 mg of sodium chloride, 0.2 - 0.4 mg of pH regulator, 0.1 - 0.3 mg of disodium hydrogen phosphate, and purified water.

[0006] In a preferred embodiment, calculated based on 5 ml of solution, it is composed of 10 mg of bromhexine hydrochloride, 52 mg of licorice extract, 135 mg of glycerol, 0.4 mg of fruit essence, 0.4 mg of sodium chloride, 0.3 mg of pH regulator, 0.2 mg of disodium hydrogen phosphate, and purified water.

[0007] In a preferred embodiment, the pH regulator includes one or more of tartaric acid, lactic acid, and citric acid.

[0008] In a preferred embodiment, the fruit essence includes one or more of orange essence, strawberry essence, and tangerine essence.

[0009] A preparation method of ambroxol hydrochloride oral liquid, comprising the following steps:

[0010] S1, raw material dissolution: Dissolve ambroxol hydrochloride in a small amount of purified water, and gently stir until completely dissolved. First dissolve the licorice extract in a small amount of purified water, and add it to the main solution after ensuring its complete dissolution;

[0011] S2, add glycerol: Add glycerol, and then stir for 8 - 10 min;

[0012] S3, add sodium chloride: Add sodium chloride to the solution, stir evenly to help adjust the osmotic pressure of the drug solution;

[0013] S4, add pH adjustment: Add a pH regulator, and continuously stir for 10 - 15 min to adjust the pH of the solution to between 5.0 - 5.5 to ensure the drug stability. Then add disodium hydrogen phosphate to further adjust the acidity and alkalinity of the solution to ensure long - term stability;

[0014] S5, add fruit essence, and then stir for 8 - 10 min;

[0015] S6, preparation: Make up the above - mentioned mixed liquid to the 5 mL scale, and continue to stir until all components are evenly mixed, with the stirring time being 10 - 15 min;

[0016] S7, filtration and packaging: Filter the solution using a sterile filter paper or a 0.45 μm filter membrane to remove any undissolved particles, and then fill the solution into a clean container.

[0017] The beneficial effects of the technical solution of the present invention are:

[0018] It can be seen from the test results of this solution that after being placed at a temperature of 25°C ± 2°C and a relative humidity of 60% ± 10% for 12 months, the total impurity content is still negligible. This indicates that the ambroxol hydrochloride oral liquid of this solution has good long - term stability and can be stored for a long time.

[0019] This solution enhances the antitussive effect by heating the licorice extract, relieves throat discomfort, improves the taste. Adding glycerol not only helps to improve the taste, but also can increase the viscosity and lubricity of the liquid medicine. At the same time, the addition of fruit essence can also improve the taste, increase acceptance, and cover up the bitterness of the drug. Specific implementation mode

[0020] The present invention will be further described in detail below. The embodiments of the present invention are given for the convenience of illustration and description, and are not exhaustive or limit the present invention to the disclosed form. Many modifications and variations are obvious to those of ordinary skill in the art. The embodiments are selected and described to better illustrate the principles and practical applications of the present invention, and enable those of ordinary skill in the art to understand the present invention and thus design various embodiments with various modifications suitable for specific purposes.

[0021] Example 1

[0022] The technical solution of the present invention provides an ambroxol hydrochloride oral solution. Calculated by 5 ml of solution, it comprises the following components: 10 mg of ambroxol hydrochloride, 52 mg of licorice extract, 135 mg of glycerol, 0.4 mg of fruit essence, 0.4 mg of sodium chloride, 0.3 mg of pH regulator, 0.2 mg of disodium hydrogen phosphate and purified water. The pH regulator comprises tartaric acid, and the fruit essence comprises orange essence.

[0023] A preparation method of an ambroxol hydrochloride oral solution comprises the following steps:

[0024] S1, raw material dissolution: Dissolve ambroxol hydrochloride in a small amount of purified water, and gently stir until completely dissolved. First dissolve the licorice extract in a small amount of purified water, and add it to the main solution after ensuring its complete dissolution. The licorice extract enhances the cough-relieving effect, relieves throat discomfort and improves the taste.

[0025] S2, adding glycerol: Add glycerol, and then stir for 8 min. Glycerol not only helps to improve the taste, but also can enhance the viscosity and lubricity of the medicinal liquid.

[0026] S3, adding sodium chloride: Add sodium chloride to the solution and stir evenly to help adjust the osmotic pressure of the drug solution.

[0027] S4, pH adjustment: Add the pH regulator and continuously stir for 10 min to adjust the pH of the solution to between 5.0 to ensure the drug stability. Then add disodium hydrogen phosphate to further adjust the acidity and alkalinity of the solution to ensure long-term stability.

[0028] S5, adding fruit essence, and then stir for 8 min.

[0029] S6, formulation: Make up the above mixed liquid to the 5 mL scale, and continue to stir until all components are evenly mixed, with a stirring time of 10 min.

[0030] S7, filtration and packaging: Filter the solution using a sterile filter paper or a 0.45 μm filter membrane to remove any undissolved particles, and then fill the solution into a clean container.

[0031] Example 2

[0032] The technical solution of the present invention provides a bromhexine hydrochloride oral solution. Calculated based on 5 ml of the solution, it includes the following components: 8 mg of bromhexine hydrochloride, 45 mg of licorice extract, 130 mg of glycerol, 0.2 mg of fruit essence, 0.3 mg of sodium chloride, 0.2 mg of pH regulator, 0.1 mg of disodium hydrogen phosphate, and purified water. The pH regulator includes lactic acid, and the fruit essence includes strawberry essence.

[0033] A preparation method of a bromhexine hydrochloride oral solution includes the following steps:

[0034] S1, Dissolution of raw materials: Dissolve bromhexine hydrochloride in a small amount of purified water, and gently stir until completely dissolved. First dissolve the licorice extract in a small amount of purified water, and add it to the main solution after ensuring its complete dissolution;

[0035] S2, Addition of glycerol: Add glycerol, and then stir for 10 min;

[0036] S3, Addition of sodium chloride: Add sodium chloride to the solution, stir evenly to help adjust the osmotic pressure of the drug solution;

[0037] S4, pH adjustment: Add the pH regulator, and continuously stir for 15 min to adjust the pH of the solution to between 5.5 to ensure the drug stability. Then add disodium hydrogen phosphate to further adjust the acidity and alkalinity of the solution to ensure long-term stability;

[0038] S5, Addition of fruit essence, and then stir for 10 min;

[0039] S6, Preparation: Make up the above mixed liquid to the 5 mL scale, and continue to stir until all components are evenly mixed, with a stirring time of 15 min;

[0040] S7, Filtration and packaging: Filter the solution using a sterile filter paper or a 0.45 μm filter membrane to remove any undissolved particles, and then fill the solution into a clean container.

[0041] Example 3

[0042] The technical solution of the present invention provides a bromhexine hydrochloride oral solution. Calculated based on 5 ml of the solution, it includes the following components: 12 mg of bromhexine hydrochloride, 55 mg of licorice extract, 150 mg of glycerol, 0.5 mg of fruit essence, 0.5 mg of sodium chloride, 0.4 mg of pH regulator, 0.3 mg of disodium hydrogen phosphate, and purified water. The pH regulator includes citric acid. The fruit essence includes orange essence.

[0043] A preparation method of a bromhexine hydrochloride oral solution includes the following steps:

[0044] S1, Dissolution of raw materials: Dissolve bromhexine hydrochloride in a small amount of purified water and stir gently until completely dissolved. First dissolve the licorice extract in a small amount of purified water, and add it to the main solution after ensuring its complete dissolution;

[0045] S2, Addition of glycerol: Add glycerol and then stir for 8 min;

[0046] S3, Addition of sodium chloride: Add sodium chloride to the solution and stir evenly to help adjust the osmotic pressure of the drug solution;

[0047] S4, pH adjustment: Add a pH regulator and continue stirring for 12 min to adjust the pH of the solution to between 5.2 to ensure drug stability. Then add disodium hydrogen phosphate to further adjust the acidity and alkalinity of the solution to ensure long-term stability;

[0048] S5, Addition of fruit essence, and then stir for 9 min;

[0049] S6, Preparation: Make up the above mixed liquid to the 5 mL mark and continue stirring until all components are evenly mixed. The stirring time is 12 min;

[0050] S7, Filtration and packaging: Filter the solution using a sterile filter paper or a 0.45 μm filter membrane to remove any undissolved particles, and then transfer the solution into a clean container.

[0051] Example 4

[0052] The technical solution of the present invention provides an oral solution of bromhexine hydrochloride. Calculated based on 5 mL of the solution, it includes the following components: 9 mg of bromhexine hydrochloride, 55 mg of licorice extract, 134 mg of glycerol, 0.4 mg of fruit essence, 0.3 mg of sodium chloride, 0.4 mg of pH regulator, 0.2 mg of disodium hydrogen phosphate, and purified water. The pH regulator includes citric acid, and the fruit essence includes orange essence.

[0053] A preparation method of an oral solution of bromhexine hydrochloride includes the following steps:

[0054] S1, Dissolution of raw materials: Dissolve bromhexine hydrochloride in a small amount of purified water and stir gently until completely dissolved. First dissolve the licorice extract in a small amount of purified water, and add it to the main solution after ensuring its complete dissolution;

[0055] S2, Addition of glycerol: Add glycerol and then stir for 10 min;

[0056] S3, Addition of sodium chloride: Add sodium chloride to the solution and stir evenly to help adjust the osmotic pressure of the drug solution;

[0057] S4, Add pH adjustment: Add a pH regulator and continuously stir for 10 min to adjust the pH of the solution to between 5.4 to ensure drug stability. Then add disodium hydrogen phosphate to further adjust the acidity and alkalinity of the solution to ensure long-term stability;

[0058] S5, Add fruit essence and then stir for 8 min;

[0059] S6, Preparation: Make up the above mixed liquid to the 5 mL mark and continue stirring until all components are evenly mixed, with a stirring time of 15 min;

[0060] S7, Filtration and packaging: Filter the solution using a sterile filter paper or a 0.45 μm filter membrane to remove any undissolved particles, and then fill the solution into a clean container.

[0061] According to the requirements of the guiding principles for stability testing in Appendix XIX C of Part II of the Chinese Pharmacopoeia 2010 Edition, the stability of the bromhexine hydrochloride oral solution prepared in Examples 1 - 4 was investigated (simulating commercial packaging, at a temperature of 25°C ± 2°C and a relative humidity of 60% ± 10%, stored for 12 months). The related substances and content were determined by high performance liquid chromatography. The results are shown in Table 1:

[0062] Table 1: Detection results of bromhexine hydrochloride oral solution

[0063] Test Items Example 1 Example 2 Example 3 Example 4 Appearance Colorless Clear Liquid Colorless Clear Liquid Colorless Clear Liquid Colorless Clear Liquid Identification Qualified Qualified Qualified Qualified pH 5.3 5.2 5.3 5.5 Related Substance A (%) Not Detected Not Detected Not Detected Not Detected Related Substance B (%) Not Detected Not Detected Not Detected Not Detected Related Substance C (%) Not Detected Not Detected Not Detected Not Detected Related Substance D (%) Not Detected Not Detected Not Detected Not Detected Related Substance E (%) 0.06 0.08 0.07 0.07 Other Maximum Impurity Not Detected Not Detected Not Detected Not Detected Total Impurity Content 0.08 0.9 0.08 0.09

[0064] From the detection results in Table 1 above, it can be seen that after being stored at a temperature of 25°C ± 2°C and a relative humidity of 60% ± 10% for 12 months, the total impurity content is still negligible. This indicates that the bromhexine hydrochloride oral solution of this solution has good long-term stability and can be stored for a long time.

[0065] Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art and related fields without creative efforts shall fall within the scope of protection of the present invention. The structures, devices, and operation methods not specifically described and explained in the present invention shall be implemented by conventional means in the art without special instructions and limitations.

Claims

1. An ambroxol hydrochloride oral solution, characterized in that, Calculated based on 5 ml of the solution, it comprises the following components: 8 - 12 mg of bromhexine hydrochloride, 45 - 55 mg of licorice extract, 130 - 150 mg of glycerol, 0.2 - 0.5 mg of fruit essence, 0.3 - 0.5 mg of sodium chloride, 0.2 - 0.4 mg of pH regulator, 0.1 - 0.3 mg of disodium hydrogen phosphate and purified water.

2. The ambroxol hydrochloride oral solution according to claim 1, wherein Calculated based on 5 ml of the solution, it comprises the following components: composed of 10 mg of bromhexine hydrochloride, 52 mg of licorice extract, 135 mg of glycerol, 0.4 mg of fruit essence, 0.4 mg of sodium chloride, 0.3 mg of pH regulator, 0.2 mg of disodium hydrogen phosphate and purified water.

3. The ambroxol hydrochloride oral solution according to claim 1, wherein The pH regulator includes one or more of tartaric acid, lactic acid, citric acid.

4. The ambroxol hydrochloride oral solution according to claim 1, wherein The fruit essence includes one or more of orange essence, strawberry essence, tangerine essence.

5. The preparation method of a bromhexine hydrochloride oral solution according to any one of claims 1-5, characterized in that, It includes the following steps: S1, raw material dissolution: Dissolve bromhexine hydrochloride in a small amount of purified water, gently stir until completely dissolved. First dissolve the licorice extract in a small amount of purified water, and add it to the main solution after ensuring its complete dissolution. S2, add glycerol: Add glycerol, and then stir for 8 - 10 min. S3, add sodium chloride: Add sodium chloride to the solution, stir evenly to help adjust the osmotic pressure of the drug solution. S4, add pH adjustment: Add the pH regulator, and continuously stir for 10 - 15 min to adjust the pH of the solution to between 5.0 - 5.5 to ensure the drug stability. Then add disodium hydrogen phosphate to further adjust the acidity and alkalinity of the solution to ensure long - term stability. S5, add fruit essence, and then stir for 8 - 10 min. S6, formulation: Make up the above - mentioned mixed liquid to 5 mL, and continue to stir until all components are evenly mixed, with the stirring time of 10 - 15 min. S7, filtration and packaging: Filter the solution using a sterile filter paper or a 0.45 μm filter membrane to remove any undissolved particles, and then fill the solution into a clean container.