Bromhexine hydrochloride oral solution
By mixing bromhexine hydrochloride with a variety of auxiliary ingredients, a bromhexine hydrochloride oral solution with excellent photothermal stability was prepared, which solved the problem of poor photothermal stability of the existing solution, improved the safety of medication and reduced transportation and storage costs.
Patent Information
- Application Number
- CN202411979771.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-31
- Publication Date
- 2025-04-22
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The existing oral solution of bromhexine hydrochloride has poor photothermal stability, which makes it difficult to ensure stability during storage and transportation, which may lead to drug safety issues and increased transportation and storage costs.
A bromhexin hydrochloride oral solution with excellent photothermal stability was prepared by mixing bromhexin hydrochloride with sucralose, glycerol, propylene glycol, polysorbate-80, fructose, sorbitol, citric acid, disodium hydrogen phosphate and water.
It improves the light and high temperature stability of bromhexine hydrochloride oral solution, reduces the stability risks during storage and transportation, ensures the safety of medication, and reduces transportation and storage costs.
Smart Images
Figure BDA0005221369840000011 
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Figure BDA0005221369840000022
Abstract
Description
Technical Field
[0001] The invention relates to the field of pharmaceutical preparations, in particular to a bromhexine hydrochloride oral solution. Background Art
[0002] Bromhexine hydrochloride is an expectorant. In clinical applications, bromhexine hydrochloride is more suitable for patients with chronic obstructive pulmonary diseases such as chronic bronchitis, emphysema, bronchiectasis, and those with sputum that is difficult to cough up. In particular, patients with shortness of breath and asthma caused by sputum blocking the small bronchi can be treated with bromhexine hydrochloride. The structural formula of bromhexine hydrochloride (CAS registration number: 611-75-6) is as follows:
[0003]
[0004] In the pharmaceutical preparation of bromhexine hydrochloride, bromhexine hydrochloride oral solution has the advantages of convenient oral administration and quick curative effect of the drug after oral administration, therefore, the patient has strong compliance to bromhexine hydrochloride oral solution, and bromhexine hydrochloride oral solution is widely used clinically. However, the existing bromhexine hydrochloride oral solution has the problem of poor light and heat stability, which makes it difficult to effectively ensure the stability of bromhexine hydrochloride oral solution during storage and transportation, thus prone to quality and safety problems, and then cause the appearance of drug safety problems, and improve transportation and storage costs, therefore, how to improve the stability of bromhexine hydrochloride oral solution is of great significance for ensuring the drug safety of bromhexine hydrochloride oral solution.
[0005] Therefore, this area needs to develop a bromhexine hydrochloride oral solution with excellent stability. Summary of the invention
[0006] The object of the present invention is to provide a bromhexine hydrochloride oral solution with excellent stability.
[0007] The first aspect of the present invention provides a bromhexine hydrochloride oral solution, which comprises bromhexine hydrochloride, sucralose, glycerol, propylene glycol, polysorbate 80, fructose, sorbitol, citric acid, disodium hydrogen phosphate and water.
[0008] Preferably, the bromhexine hydrochloride is 0.1-0.3 parts by weight, more preferably 0.15-0.25 parts by weight, more preferably 0.18-0.22 parts by weight, and most preferably 0.2 parts by weight.
[0009] Preferably, the content of bromhexine hydrochloride is 0.1-0.3 g / 100 ml, preferably 0.15-0.25 g / 100 ml, more preferably 0.18-0.22 g / 100 ml, and most preferably 0.2 g / 100 ml.
[0010] Preferably, the sucralose is 0.05-0.2 parts by weight, more preferably 0.08-0.16 parts by weight, more preferably 0.10-0.14 parts by weight, and most preferably 0.12 parts by weight.
[0011] Preferably, the content of sucralose is 0.05-0.2 g / 100 ml, more preferably 0.08-0.16 g / 100 ml, more preferably 0.10-0.14 g / 100 ml, and most preferably 0.12 g / 100 ml.
[0012] Preferably, the glycerol is 0.3-1.5 parts by weight, more preferably 0.4-1.2 parts by weight, more preferably 0.6-1.0 parts by weight, and most preferably 0.8 parts by weight.
[0013] Preferably, the content of glycerol is 0.3-1.5 g / 100 ml, more preferably 0.4-1.2 g / 100 ml, more preferably 0.6-1.0 g / 100 ml, and most preferably 0.8 g / 100 ml.
[0014] Preferably, the propylene glycol is 0.5-2.5 parts by weight, more preferably 1.0-2.0 parts by weight, more preferably 1.3-1.7 parts by weight, and most preferably 1.5 parts by weight.
[0015] Preferably, the content of propylene glycol is 0.5-2.5 g / 100 ml, more preferably 1.0-2.0 g / 100 ml, more preferably 1.3-1.7 g / 100 ml, and most preferably 1.5 g / 100 ml.
[0016] Preferably, the polysorbate 80 is 0.1-0.8 parts by weight, more preferably 0.2-0.6 parts by weight, more preferably 0.3-0.5 parts by weight, and most preferably 0.4 parts by weight.
[0017] Preferably, the content of polysorbate 80 is 0.1-0.8 g / 100 ml, more preferably 0.2-0.6 g / 100 ml, more preferably 0.3-0.5 g / 100 ml, and most preferably 0.4 g / 100 ml.
[0018] Preferably, the fructose is 0.2-2.0 parts by weight, more preferably 0.5-1.5 parts by weight, more preferably 0.8-1.2 parts by weight, and most preferably 1.0 parts by weight.
[0019] Preferably, the fructose content is 0.2-2.0 g / 100 ml, more preferably 0.5-1.5 g / 100 ml, more preferably 0.8-1.2 g / 100 ml, and most preferably 1.0 g / 100 ml.
[0020] Preferably, the sorbitol is 0.5-2.5 parts by weight, more preferably 1.0-2.0 parts by weight, more preferably 1.3-1.7 parts by weight, and most preferably 1.5 parts by weight.
[0021] Preferably, the content of sorbitol is 0.5-2.5 g / 100 ml, more preferably 1.0-2.0 g / 100 ml, more preferably 1.3-1.7 g / 100 ml, and most preferably 1.5 g / 100 ml.
[0022] Preferably, the citric acid is 0.8-1.8 parts by weight, more preferably 1.0-1.6 parts by weight, more preferably 1.1-1.5 parts by weight, and most preferably 1.3 parts by weight.
[0023] Preferably, the content of citric acid is 0.8-1.8 g / 100 ml, more preferably 1.0-1.6 g / 100 ml, more preferably 1.1-1.5 g / 100 ml, and most preferably 1.3 g / 100 ml.
[0024] Preferably, the disodium hydrogen phosphate is 2-4 parts by weight, more preferably 2.4-3.2 parts by weight, more preferably 2.6-3.0 parts by weight, and most preferably 2.8 parts by weight.
[0025] Preferably, the content of disodium hydrogen phosphate is 2-4 g / 100 ml, more preferably 2.4-3.2 g / 100 ml, more preferably 2.6-3.0 g / 100 ml, and most preferably 2.8 g / 100 ml.
[0026] Preferably, the water is 80-120 parts by weight, more preferably 90-110 parts by weight, more preferably 95-105 parts by weight, and most preferably 100 parts by weight.
[0027] Preferably, the water comprises purified water.
[0028] Preferably, the bromhexine hydrochloride oral solution comprises:
[0029]
[0030] Preferably, the bromhexine hydrochloride oral solution comprises:
[0031]
[0032]
[0033] Preferably, the bromhexine hydrochloride oral solution comprises:
[0034]
[0035] Preferably, the bromhexine hydrochloride oral solution comprises:
[0036]
[0037] Preferably, the bromhexine hydrochloride oral solution comprises:
[0038]
[0039] The second aspect of the present invention provides a method for preparing the bromhexine hydrochloride oral solution as described in the first aspect of the present invention, wherein the method comprises the steps of:
[0040] The bromhexine hydrochloride oral solution is obtained by mixing bromhexine hydrochloride, sucralose, glycerol, propylene glycol, polysorbate 80, fructose, sorbitol, citric acid, disodium hydrogen phosphate and water.
[0041] Preferably, the bromhexine hydrochloride oral solution is prepared by the following method:
[0042] Take 75-85% of the prescribed amount of water after boiling and cooling, add the prescribed amount of glycerol and the prescribed amount of propylene glycol, stir and mix, add the prescribed amount of bromhexine hydrochloride and the prescribed amount of polysorbate-80, stir and mix, add the prescribed amount of sucralose, the prescribed amount of fructose, the prescribed amount of sorbitol, the prescribed amount of citric acid and the prescribed amount of disodium hydrogen phosphate, stir and mix, add the boiled and cooled water to make up the volume to the dispensing volume, stir and mix, filter, and obtain the bromhexine hydrochloride oral solution.
[0043] Preferably, the stirring and mixing temperature is 35-45°C, more preferably 38-42°C, more preferably 40°C.
[0044] Preferably, the filtering comprises filtering through 0.45 μm and 0.22 μm microporous membranes in sequence.
[0045] The third aspect of the present invention provides a medicine kit, wherein the medicine kit comprises the bromhexine hydrochloride oral solution as described in the first aspect of the present invention.
[0046] Preferably, the medicine box further comprises a transparent container.
[0047] Preferably, the transparent container comprises a transparent PET bottle.
[0048] Preferably, the bromhexine hydrochloride oral solution is packaged in the transparent container.
[0049] The fourth aspect of the present invention provides a use of the bromhexine hydrochloride oral solution as described in the first aspect of the present invention for preparing an expectorant medicament.
[0050] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described below (such as embodiments) can be combined with each other to form new or preferred technical solutions. DETAILED DESCRIPTION
[0051] The invention discloses a bromhexine hydrochloride oral solution, which comprises bromhexine hydrochloride, sucralose, glycerol, propylene glycol, polysorbate 80, fructose, sorbitol, citric acid, disodium hydrogen phosphate and water. The bromhexine hydrochloride oral solution composed of specific components of the invention has excellent light and high temperature stability, improves the storage and transportation stability of the bromhexine hydrochloride oral solution, reduces the storage and transportation costs, and ensures the quality and safety of the bromhexine hydrochloride oral solution.
[0052] the term
[0053] As used herein, the terms "comprise", "include", and "contain" are used interchangeably and include not only closed definitions, but also semi-closed and open definitions. In other words, the terms include "consisting of", "consisting essentially of".
[0054] As used herein, polysorbate 80 is polysorbate 80, also known as Tween 80.
[0055] As used herein, the term "PET" refers to polyethylene terephthalate, also known as Poly (ethylene Terephthalate) in English.
[0056] As used herein, the term "parts by weight" can be any fixed weight expressed in milligrams, grams or kilograms (such as 1 mg, 1 g or 1 kg, etc.). For example, a composition consisting of 1 part by weight of component a and 9 parts by weight of component b can be a composition consisting of 1 gram of component a + 9 grams of component b, or 10 grams of component a + 90 grams of component b, etc. In the bromhexine hydrochloride oral solution, the percentage content of a component = (the weight parts of the component / the sum of the weight parts of all components) × 100%. For example, in a composition consisting of 1 part by weight of component a and 9 parts by weight of component b, the content of component a is 10%, and the content of component b is 90%.
[0057] Bromhexine Hydrochloride Oral Solution
[0058] The invention provides a bromhexine hydrochloride oral solution with excellent light and heat stability, thereby ensuring the quality safety of the bromhexine hydrochloride oral solution.
[0059] The bromhexine hydrochloride oral solution of the present invention may include (but not limited to) bromhexine hydrochloride, sucralose, glycerol, propylene glycol, polysorbate-80, fructose, sorbitol, citric acid, disodium hydrogen phosphate and water.
[0060] In a preferred embodiment of the present invention, the bromhexine hydrochloride oral solution comprises:
[0061]
[0062] Preferably, the bromhexine hydrochloride oral solution comprises:
[0063]
[0064] Typically, the bromhexine hydrochloride oral solution comprises:
[0065]
[0066] Specifically, the bromhexine hydrochloride oral solution of the present invention is as described above in the first aspect of the present invention.
[0067] The bromhexine hydrochloride oral solution of the present invention can be prepared by a mixing method, for example, by mixing bromhexine hydrochloride, sucralose, glycerol, propylene glycol, polysorbate 80, fructose, sorbitol, citric acid, disodium hydrogen phosphate and water to obtain the bromhexine hydrochloride oral solution.
[0068] use
[0069] The present invention also provides a use of the bromhexine hydrochloride oral solution of the present invention in preparing expectorant medicines.
[0070] The main excellent technical effects of the present invention include:
[0071] The invention develops a bromhexine hydrochloride oral solution. The bromhexine hydrochloride oral solution has excellent light and high temperature stability, improves the storage and transportation stability of the bromhexine hydrochloride oral solution, reduces the storage and transportation costs, and ensures the quality safety of the bromhexine hydrochloride oral solution.
[0072] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples where specific conditions are not specified are usually based on conventional conditions.
[0073] Example 1 Bromhexine hydrochloride oral solution
[0074] This embodiment 1 prepares a bromhexine hydrochloride oral solution, and the prescription composition of the bromhexine hydrochloride oral solution is shown in Table 1:
[0075] Table 1 Prescription composition of bromhexine hydrochloride oral solution
[0076] Components Dosage Bromhexine Hydrochloride 0.2g Sucralose 0.12g glycerin 0.8g Propylene glycol 1.5g Polysorbate-80 0.4g fructose 1.0g Sorbitol 1.5g Citric acid 1.3g Disodium hydrogen phosphate 2.8g Add purified water Up to 100ml.
[0077] Preparation method:
[0078] Take 80% of the prescribed amount of purified water after boiling and cooling, add the prescribed amount of glycerol and the prescribed amount of propylene glycol, stir and mix at 40°C, add the prescribed amount of bromhexine hydrochloride and the prescribed amount of polysorbate-80, stir and mix at 40°C, add the prescribed amount of sucralose, the prescribed amount of fructose, the prescribed amount of sorbitol, the prescribed amount of citric acid and the prescribed amount of disodium hydrogen phosphate, stir and mix at 40°C, add the boiled and cooled purified water to make up to the dispensing volume, stir and mix, filter through 0.45μm and 0.22μm microporous filter membranes in sequence to obtain bromhexine hydrochloride oral solution.
[0079] Comparative Example 1 Bromhexine Hydrochloride Oral Solution
[0080] This comparative example 1 prepares a bromhexine hydrochloride oral solution, and the prescription composition of the bromhexine hydrochloride oral solution is shown in Table 2:
[0081] Table 2 Prescription composition of bromhexine hydrochloride oral solution
[0082]
[0083]
[0084] Preparation method:
[0085] Take 80% of the prescribed amount of purified water after boiling and cooling, add the prescribed amount of glycerol and the prescribed amount of propylene glycol, stir and mix at 40°C, add the prescribed amount of bromhexine hydrochloride and the prescribed amount of polysorbate-80, stir and mix at 40°C, add the prescribed amount of sucralose, the prescribed amount of fructose, the prescribed amount of sorbitol, the prescribed amount of citric acid and the prescribed amount of disodium hydrogen phosphate, stir and mix at 40°C, add the boiled and cooled purified water to make up to the dispensing volume, stir and mix, filter through 0.45μm and 0.22μm microporous filter membranes in sequence to obtain bromhexine hydrochloride oral solution.
[0086] Comparative Example 2 Bromhexine Hydrochloride Oral Solution
[0087] This comparative example 2 prepares a bromhexine hydrochloride oral solution, and the prescription composition of the bromhexine hydrochloride oral solution is shown in Table 3:
[0088] Table 3 Prescription composition of bromhexine hydrochloride oral solution
[0089] Components Dosage Bromhexine Hydrochloride 0.2g Sucralose 0.12g glycerin 0.8g Polysorbate-80 0.4g fructose 1.0g Sorbitol 1.0g Citric acid 1.3g Disodium hydrogen phosphate 2.8g Add purified water Up to 100ml.
[0090] Preparation method:
[0091] Take 80% of the prescribed amount of purified water after boiling and cooling, add the prescribed amount of glycerol, stir and mix at 40°C, add the prescribed amount of bromhexine hydrochloride and the prescribed amount of polysorbate-80, stir and mix at 40°C, add the prescribed amount of sucralose, the prescribed amount of fructose, the prescribed amount of sorbitol, the prescribed amount of citric acid and the prescribed amount of disodium hydrogen phosphate, stir and mix at 40°C, add the boiled and cooled purified water to make up to the dispensing volume, stir and mix, filter through 0.45μm and 0.22μm microporous filter membranes in sequence to obtain bromhexine hydrochloride oral solution.
[0092] Comparative Example 3 Bromhexine Hydrochloride Oral Solution
[0093] This comparative example 3 prepares a bromhexine hydrochloride oral solution, and the prescription composition of the bromhexine hydrochloride oral solution is shown in Table 4:
[0094] Table 4 Prescription composition of bromhexine hydrochloride oral solution
[0095]
[0096]
[0097] Preparation method:
[0098] Take 80% of the prescribed amount of purified water after boiling and cooling, add the prescribed amount of glycerol and the prescribed amount of polyethylene glycol 400, stir and mix at 40°C, add the prescribed amount of bromhexine hydrochloride and the prescribed amount of polysorbate-80, stir and mix at 40°C, add the prescribed amount of sucralose, the prescribed amount of fructose, the prescribed amount of sorbitol, the prescribed amount of citric acid and the prescribed amount of disodium hydrogen phosphate, stir and mix at 40°C, add the boiled and cooled purified water to make up to the dispensing volume, stir and mix, filter through 0.45μm and 0.22μm microporous filter membranes in sequence to obtain bromhexine hydrochloride oral solution.
[0099] Stability test
[0100] 1. Investigation on the stability of light factors
[0101] According to the guidance of the stability test of preparations in the Chinese Pharmacopoeia, the bromhexine hydrochloride oral solution prepared in Example 1 and Comparative Examples 1-3 and packaged in transparent PET bottles was examined under illumination conditions (4500lx, 25°C) for 0 days, 10 days and 30 days, and the appearance properties of the bromhexine hydrochloride oral solution at different time points were examined. The bromhexine hydrochloride content and total impurity content of the bromhexine hydrochloride oral solution were determined by high performance liquid chromatography. The results of the light stability examination of the bromhexine hydrochloride oral solution prepared in Example 1 and Comparative Examples 1-3 are shown in Table 5.
[0102] Table 5 Stability of bromhexine hydrochloride oral solution prepared in Example 1 and Comparative Examples 1-3 under illumination conditions (4500lx, 25°C)
[0103]
[0104] As can be seen from Table 5, the bromhexine hydrochloride oral solution prepared in Example 1 has excellent light stability, can improve the stability during transportation and storage, reduce transportation and storage costs, and ensure the quality and safety of the bromhexine hydrochloride oral solution.
[0105] 2. Accelerated stability test
[0106] According to the guidelines for the stability test of preparations in the Chinese Pharmacopoeia, the bromhexine hydrochloride oral solution prepared in Example 1 and packaged in a transparent PET bottle was tested at a temperature of 40±2°C and a relative humidity of RH 75±5% for 0 days, 1, 3 and 6 months. The appearance properties of the bromhexine hydrochloride oral solution at different time points were tested, and the bromhexine hydrochloride content and total impurity content of the bromhexine hydrochloride oral solution were determined by high performance liquid chromatography. The results of the accelerated stability test of the bromhexine hydrochloride oral solution prepared in Example 1 are shown in Table 6.
[0107] Table 6 Stability study of bromhexine hydrochloride oral solution prepared in Example 1 under accelerated conditions (40±2°C, RH 75±5%)
[0108]
[0109] As can be seen from Table 6, the bromhexine hydrochloride oral solution prepared in Example 1 has excellent high temperature and high humidity stability, can improve the stability during transportation and storage, reduce transportation and storage costs, and ensure the quality and safety of the bromhexine hydrochloride oral solution.
[0110] The above is an implementation scheme of the present invention designed for a case. It should be pointed out that for ordinary technicians in this technical field, several improvements can be made without departing from the principle of the present invention, and these improvements should also be regarded as the scope of protection of the present invention.
Claims
1. A bromhexine hydrochloride oral solution, characterized in that, The bromhexine hydrochloride oral solution comprises bromhexine hydrochloride, sucralose, glycerol, propylene glycol, polysorbate-80, fructose, sorbitol, citric acid, disodium hydrogen phosphate and water.
2. Bromhexine hydrochloride oral solution as claimed in claim 1, characterized in that, The bromhexine hydrochloride is 0.1-0.3 parts by weight, preferably 0.15-0.25 parts by weight, more preferably 0.18-0.22 parts by weight, and most preferably 0.2 parts by weight; The sucralose is 0.05-0.2 parts by weight, preferably 0.08-0.16 parts by weight, more preferably 0.10-0.14 parts by weight, and most preferably 0.12 parts by weight; The glycerol is 0.3-1.5 parts by weight, preferably 0.4-1.2 parts by weight, more preferably 0.6-1.0 parts by weight, and most preferably 0.8 parts by weight; The propylene glycol is 0.5-2.5 parts by weight, preferably 1.0-2.0 parts by weight, more preferably 1.3-1.7 parts by weight, and most preferably 1.5 parts by weight; The polysorbate 80 is 0.1-0.8 parts by weight, preferably 0.2-0.6 parts by weight, more preferably 0.3-0.5 parts by weight, and most preferably 0.4 parts by weight; The fructose is 0.2-2.0 parts by weight, preferably 0.5-1.5 parts by weight, more preferably 0.8-1.2 parts by weight, and most preferably 1.0 parts by weight; The sorbitol is 0.5-2.5 parts by weight, preferably 1.0-2.0 parts by weight, more preferably 1.3-1.7 parts by weight, and most preferably 1.5 parts by weight; The citric acid is 0.8-1.8 parts by weight, preferably 1.0-1.6 parts by weight, more preferably 1.1-1.5 parts by weight, and most preferably 1.3 parts by weight; The disodium hydrogen phosphate is 2-4 parts by weight, preferably 2.4-3.2 parts by weight, more preferably 2.6-3.0 parts by weight, and most preferably 2.8 parts by weight; and The water is 80-120 parts by weight, preferably 90-110 parts by weight, more preferably 95-105 parts by weight, and most preferably 100 parts by weight.
3. Bromhexine hydrochloride oral solution as claimed in claim 1, characterized in that, Described bromhexine hydrochloride oral solution comprises:
4. Bromhexine hydrochloride oral solution as claimed in claim 1, characterized in that, Described bromhexine hydrochloride oral solution comprises:
5. Bromhexine hydrochloride oral solution as claimed in claim 1, characterized in that, Described bromhexine hydrochloride oral solution comprises:
6. Bromhexine hydrochloride oral solution as claimed in claim 1, characterized in that, Described bromhexine hydrochloride oral solution comprises:
7. Bromhexine hydrochloride oral solution as claimed in claim 1, characterized in that, Described bromhexine hydrochloride oral solution comprises:
8. A method for preparing the bromhexine hydrochloride oral solution as claimed in claim 1, wherein the method comprises the steps of: The bromhexine hydrochloride oral solution is obtained by mixing bromhexine hydrochloride, sucralose, glycerol, propylene glycol, polysorbate 80, fructose, sorbitol, citric acid, disodium hydrogen phosphate and water.
9. A medicine box, characterized in that: The medicine box comprises the bromhexine hydrochloride oral solution as claimed in claim 1.
10. Use of the bromhexine hydrochloride oral solution as claimed in claim 1 for preparing expectorant medicine.