CN114533664B - Compound oral liquid preparation of dextromethorphan hydrobromide and guaiacol glyceryl ether - Google Patents
Compound oral liquid preparation of dextromethorphan hydrobromide and guaiacol glyceryl ether Download PDFInfo
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Abstract
The invention relates to a compound oral liquid preparation of dextromethorphan hydrobromide and guaiacol glyceryl ether. The compound oral solution comprises dextromethorphan hydrobromide, guaifenesin, a flavoring agent, a stabilizing agent and a solvent. The dextromethorphan hydrobromide and guaifenesin compound oral solution has excellent mouthfeel and stability.
Description
Technical Field
The invention relates to the field of medicinal preparations, in particular to a compound oral liquid preparation of dextromethorphan hydrobromide and guaiacol glyceryl ether.
Background
The combination of dextromethorphan hydrobromide and guaifenesin can be used for effectively treating cough and expectoration caused by upper respiratory tract infection (such as common cold and influenza), bronchitis and the like. The structural formulas of dextromethorphan hydrobromide and guaiacol glyceryl ether are as follows:
the existing clinic often uses liquid preparation containing dextromethorphan hydrobromide and guaifenesin, such as syrup, to treat cough and expectoration. The dextromethorphan hydrobromide and guaiacol glyceryl ether compound oral liquid preparation has convenient taking and good content uniformity, and can quickly exert the drug treatment effect after being taken.
However, the existing compound oral liquid preparation of dextromethorphan and guaiacol glyceryl ether still has many disadvantages, for example, bitter taste and residual bitter taste problems exist after the oral administration of the dextromethorphan hydrobromide and guaiacol glyceryl ether compound oral liquid preparation, which causes poor oral compliance of patients, especially children, although the sweet taste of the compound oral liquid preparation is increased by adding a sweetening agent to improve the taste, the bitter taste and residual bitter taste problems still exist even if the sweetening agent is added, in order to further overcome the bitter taste of the oral liquid preparation, the existing compound oral liquid preparation usually improves the flavor of the oral liquid by adding a plurality of essences such as orange essence, apricot essence, lemon essence and the like to cover the bitter taste, however, the residual bitter taste problem still exists even if the essences are added, and the essences have toxic action and are not beneficial to the health of human bodies, especially to children with incomplete development. In addition, the dextromethorphan and guaiacol glyceryl ether compound oral liquid preparation is easily influenced by various factors, such as light, heat and the like, so that the content is reduced, impurities are increased, precipitation and crystallization phenomena are easy to occur, and the stability is poor, therefore, in order to improve the stability of the existing dextromethorphan and guaiacol glyceryl ether compound oral liquid preparation on the market, the dextromethorphan and guaiacol glyceryl ether compound oral liquid preparation is filled in a brown bottle, a large amount of preservative is added, and the storage needs to be performed in a shading and high-temperature avoiding manner, so that the packaging, transportation and storage costs of the dextromethorphan and guaiacol glyceryl ether liquid preparation are increased, and the properties of the dextromethorphan and guaiacol glyceryl ether liquid preparation, such as the clarity, whether precipitation particles, mildew, acid, discoloration, foreign matters, gas generation and other deterioration phenomena exist in the brown bottle are difficult to be simply and effectively observed by a patient before purchasing or using the dextromethorphan and guaiacol glyceryl ether liquid preparation, and the problem of medicine use safety is easily caused. In addition, the existing dextromethorphan and guaiacol glycerol ether compound syrup contains a large amount of sucrose, and is not suitable for patients with hyperglycemia and diabetes mellitus.
Therefore, there is a need in the art to develop a compound oral liquid preparation of dextromethorphan and guaiacol glyceryl ether with excellent mouthfeel and stability, and to improve the oral compliance and safety of the compound oral liquid preparation of dextromethorphan and guaiacol glyceryl ether.
Disclosure of Invention
The invention aims to provide a dextromethorphan hydrobromide and guaiacol glyceryl ether compound oral liquid preparation with excellent mouthfeel and stability.
In a first aspect of the invention, a compound oral liquid preparation is provided, which comprises dextromethorphan hydrobromide, guaifenesin, a flavoring agent, a stabilizer and a solvent.
Preferably, the oral liquid preparation is a compound oral solution.
Preferably, the dextromethorphan hydrobromide is present in an amount of 0.1 to 0.5wt%, more preferably 0.2 to 0.4wt%, more preferably 0.25 to 0.35wt%, more preferably 0.28 to 0.32wt%, most preferably 0.3wt%, based on the weight of the liquid combination oral preparation.
Preferably, the dextromethorphan hydrobromide is 0.1 to 0.5 parts by weight, more preferably 0.2 to 0.4 parts by weight, more preferably 0.25 to 0.35 parts by weight, more preferably 0.28 to 0.32 parts by weight, most preferably 0.3 parts by weight.
Preferably, the content of guaifenesin is 0.5-5wt%, more preferably 1-3wt%, more preferably 1.5-2.5wt%, more preferably 1.8-2.2wt%, most preferably 2wt%, based on the weight of the compound oral liquid preparation.
Preferably, the guaifenesin is present in an amount of 0.5 to 5 parts by weight, more preferably 1 to 3 parts by weight, more preferably 1.5 to 2.5 parts by weight, more preferably 1.8 to 2.2 parts by weight, most preferably 2 parts by weight.
Preferably, the flavoring agent comprises sucralose, sorbitol, xylitol, and fructose.
Preferably, the sucralose is contained in an amount of 0.05 to 0.5wt%, more preferably 0.05 to 0.2wt%, more preferably 0.05 to 0.15wt%, more preferably 0.08 to 0.12wt%, most preferably 0.1wt%, based on the weight of the compound oral liquid preparation.
Preferably, the sucralose is 0.05 to 0.5 parts by weight, more preferably 0.05 to 0.2 parts by weight, more preferably 0.05 to 0.15 parts by weight, more preferably 0.08 to 0.12 parts by weight, most preferably 0.1 parts by weight.
Preferably, the sorbitol is present in an amount of 3-20wt%, more preferably 5-15wt%, more preferably 6-10wt%, more preferably 7-9wt%, most preferably 8wt%, based on the weight of the combination oral liquid formulation.
Preferably, the sorbitol is present in an amount of 3 to 20 parts by weight, more preferably 5 to 15 parts by weight, more preferably 6 to 10 parts by weight, more preferably 7 to 9 parts by weight, most preferably 8 parts by weight.
Preferably, the content of xylitol is 3-20wt%, more preferably 5-15wt%, more preferably 6-10wt%, more preferably 7-9wt%, most preferably 8wt%, based on the weight of the compound oral liquid preparation.
Preferably, the xylitol is present in an amount of 3 to 20 parts by weight, more preferably 5 to 15 parts by weight, more preferably 6 to 10 parts by weight, more preferably 7 to 9 parts by weight, most preferably 8 parts by weight.
Preferably, the fructose is present in an amount of 5 to 25wt%, more preferably 5 to 20wt%, more preferably 10 to 15wt%, more preferably 11 to 13wt%, most preferably 12wt%, based on the weight of the complex oral liquid formulation.
Preferably, the fructose is 5 to 25 parts by weight, more preferably 5 to 20 parts by weight, more preferably 10 to 15 parts by weight, more preferably 11 to 13 parts by weight, most preferably 12 parts by weight.
Preferably, the weight ratio of said fructose to said xylitol is from 1 to 2, preferably from 1.3 to 1.7, more preferably 1.5.
Preferably, the stabilizer comprises hydroxyethyl cellulose and glycine.
Preferably, the content of the hydroxyethyl cellulose is 0.2-1.0wt%, more preferably 0.2-0.8wt%, more preferably 0.2-0.6wt%, more preferably 0.3-0.5wt%, most preferably 0.4wt%, based on the weight of the compound oral liquid preparation.
Preferably, the hydroxyethyl cellulose is 0.2 to 1.0 parts by weight, more preferably 0.2 to 0.8 parts by weight, more preferably 0.2 to 0.6 parts by weight, more preferably 0.3 to 0.5 parts by weight, most preferably 0.4 parts by weight.
Preferably, the glycine is present in an amount of 0.1 to 1.0wt%, more preferably 0.1 to 0.8wt%, more preferably 0.1 to 0.5wt%, more preferably 0.2 to 0.4wt%, most preferably 0.3wt%, based on the weight of the combination oral liquid formulation.
Preferably, the glycine is present in an amount of 0.1 to 1.0 parts by weight, more preferably 0.1 to 0.8 parts by weight, more preferably 0.1 to 0.5 parts by weight, more preferably 0.2 to 0.4 parts by weight, most preferably 0.3 parts by weight.
Preferably, the solvent includes water, ethanol and glycerol.
Preferably, the ethanol is present in an amount of 2 to 7wt%, more preferably 3 to 5wt%, more preferably 3.5 to 4.5wt%, more preferably 3.8 to 4.2wt%, and most preferably 4wt%, based on the weight of the liquid combination oral formulation.
Preferably, the ethanol is 2 to 7 parts by weight, more preferably 3 to 5 parts by weight, more preferably 3.5 to 4.5 parts by weight, more preferably 3.8 to 4.2 parts by weight, most preferably 4 parts by weight.
Preferably, the glycerol is present in an amount of 4-8wt%, more preferably 5-7wt%, more preferably 5.5-6.5wt%, more preferably 5.8-6.2wt%, most preferably 6wt%, based on the weight of the liquid combination oral formulation.
Preferably, the glycerol is present in an amount of 4 to 8 parts by weight, more preferably 5 to 7 parts by weight, more preferably 5.5 to 6.5 parts by weight, more preferably 5.8 to 6.2 parts by weight, most preferably 6 parts by weight.
Preferably, the water is purified water or water for injection.
Preferably, the amount of water is 70 to 120 parts by weight, preferably 80 to 110 parts by weight, more preferably 80 to 100 parts by weight, still more preferably 85 to 100 parts by weight, most preferably 85 to 95 parts by weight.
Preferably, the compound oral liquid preparation comprises dextromethorphan hydrobromide, guaifenesin, sucralose, sorbitol, xylitol, fructose, hydroxyethyl cellulose, glycine, ethanol, glycerol and water.
Preferably, the compound oral liquid preparation comprises:
| components | Dosage of |
| Dextromethorphan hydrobromide | 0.2 to 0.4 part by weight |
| Guaifenesin | 1 to 3 parts by weight of |
| Sucralose | 0.05-0.15 weight part |
| Ethanol | 2-6 parts by weight |
| Glycerol | 4 to 8 parts by weight of |
| Sorbitol | 6 to 10 parts by weight of |
| Xylitol, its preparation method and use | 6 to 10 parts by weight of |
| Fructose | 10 to 14 portions of |
| Hydroxyethyl cellulose | 0.2 to 0.6 part by weight |
| Glycine | 0.1-0.5 weight parts; and |
| water (I) | 85-100 parts by weight. |
Preferably, the compound oral liquid preparation comprises:
preferably, the compound oral liquid preparation comprises:
| components | Dosage of |
| Dextromethorphan hydrobromide | 0.3 part by weight |
| Guaifenesin | 2.0 parts by weight |
| Sucralose | 0.1 part by weight |
| Ethanol | 4.0 parts by weight |
| Glycerol | 6.0 parts by weight |
| Sorbitol | 8.0 parts by weight |
| Xylitol, its preparation method and use | 8.0 parts by weight |
| Fructose | 12.0 parts by weight |
| Hydroxyethyl cellulose | 0.4 part by weight |
| Glycine | 0.3 part by weight; and |
| water (W) | 85 to 95 weight portions. |
Preferably, the compound oral liquid preparation comprises:
| components | Amount of the composition |
| Dextromethorphan hydrobromide | 0.3g |
| Guaifenesin | 2.0g |
| Sucralose | 0.1g |
| Ethanol | 4.0g |
| Glycerol | 6.0g |
| Sorbitol | 8.0g |
| Xylitol, its preparation method and application | 8.0g |
| Fructose | 12.0g |
| Hydroxyethyl cellulose | 0.4g |
| Glycine | 0.3g |
| Water (W) | To 100ml. |
Preferably, the unit of parts by weight is g.
Preferably, the compound oral liquid preparation is subpackaged in transparent containers.
Preferably, the transparent container comprises a transparent plastic container or a transparent glass container.
Preferably, the transparent plastic container comprises a transparent PET bottle.
In a second aspect of the present invention, there is provided a method for preparing the complex oral liquid formulation according to the first aspect of the present invention, the method comprising the steps of:
mixing dextromethorphan hydrobromide, guaiacol glyceryl ether, a flavoring agent, a stabilizing agent and a solvent to obtain the compound oral liquid preparation.
Preferably, the method comprises the steps of:
mixing dextromethorphan hydrobromide, guaiacol glyceryl ether, sucralose, sorbitol, xylitol, fructose, hydroxyethyl cellulose, glycine, ethanol, glycerol and water to obtain the compound oral liquid preparation.
In another preferred embodiment, after mixing, filtering through a microporous membrane to obtain the compound oral liquid preparation.
Preferably, the compound oral liquid preparation is prepared by the following method:
adding ethanol and glycerol into 75-85% of water according to the formula amount, stirring and mixing, adding dextromethorphan hydrobromide and guaiacol glyceryl ether, stirring and mixing at 45-55 ℃, adding hydroxyethyl cellulose, stirring and mixing at 45-55 ℃, then adding sucralose, sorbitol, xylitol, fructose and glycine, stirring and mixing at 45-55 ℃, adding the rest of water according to the formula amount to a fixed volume, and filtering through a microporous filter membrane to obtain the compound oral solution.
Preferably, the size of the filtration pores of the microporous filtration membrane is 0.10 to 1.0 μm, preferably 0.22 μm, 0.45 μm or 0.80 μm.
In a third aspect of the present invention, there is provided a kit comprising a transparent container and a compound oral liquid formulation according to the first aspect of the present invention.
Preferably, the compound oral liquid preparation is separately packaged in the transparent container.
Preferably, the transparent container contains the compound oral liquid preparation according to the first aspect of the invention.
Preferably, the transparent container comprises a transparent plastic container or a transparent glass container.
Preferably, the transparent plastic container comprises a transparent PET bottle.
In a fourth aspect of the present invention, there is provided a use of the compound oral liquid formulation according to the first aspect of the present invention for the preparation of a medicament for preventing cough and expectoration caused by upper respiratory tract infection, bronchitis, and the like.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments.
Detailed Description
The invention provides a compound oral liquid preparation which has excellent mouthfeel and high oral compliance of patients, and the compound oral liquid preparation has excellent light and heat stability, thereby being convenient for packaging, storage and transportation. In addition, the compound oral liquid preparation does not contain sucrose and glucose which cause rapid rise of blood sugar, and is suitable for patients with hyperglycemia and diabetes to take, so that the people taking the compound oral liquid preparation are expanded.
Term(s) for
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
As used herein, the terms "comprises," "comprising," "includes," "including," and "including" are used interchangeably and include not only closed-form definitions, but also semi-closed and open-form definitions. In other words, the term includes "consisting of 8230; \8230; composition;" consisting essentially of 8230; \8230; composition 8230).
In the pharmaceutical composition of the present invention, the weight content (wt%) or concentration (e.g., μ g/mL) of each component is based on the weight or volume of the pharmaceutical composition.
The term "glycerol" as used herein refers to 1,2, 3-propanetriol.
As used herein, the term "hydroxyethylcellulose" has a CAS number of 9004-62-0.
As used herein, the term "fructose" has a CAS number of 57-48-7.
As used herein, the term "PET" refers to polyester, and "pharmaceutical polyester bottles" and "pharmaceutical PET bottles" are used slowly.
As used herein, the term "part by weight" can be any fixed weight expressed in milligrams, grams, or kilograms (e.g., 1mg, 1g, or 1kg, etc.). For example, a composition consisting of 1 part by weight of component a and 9 parts by weight of component b may be a composition consisting of 1g of component a +9 g of component b, or 10 g of component a +90 g of component b. In the pharmaceutical composition, the percentage content of a certain component = (parts by weight of the component/sum of parts by weight of all components) × 100%, and thus, in a composition composed of 1 part by weight of the component a and 9 parts by weight of the component b, the content of the component a is 10% and the content of the component b is 90%.
Compound oral liquid preparation and preparation method thereof
The invention provides a compound oral liquid preparation, which comprises dextromethorphan hydrobromide, guaifenesin, a flavoring agent, a stabilizing agent and a solvent.
The compound oral liquid preparation can be subpackaged in transparent containers. The transparent container comprises a transparent plastic (such as PET) container or a transparent glass container.
Specifically, the compound oral liquid preparation of the present invention is as described above in the first aspect of the present invention.
Typically, the compound oral liquid preparation comprises:
| components | Amount of the composition |
| Dextromethorphan hydrobromide | 0.2 to 0.4 portion by weight |
| Guaiacol glyceryl ether | 1 to 3 parts by weight of |
| Sucralose | 0.05-0.15 weight part |
| Ethanol | 2-6 parts by weight |
| Glycerol | 4 to 8 portions of |
| Sorbitol | 6 to 10 parts by weight of |
| Xylitol, its preparation method and application | 6 to 10 parts by weight of |
| Fructose | 10 to 14 parts by weight of |
| Hydroxyethyl cellulose | 0.2 to 0.6 part by weight |
| Glycine | 0.1-0.5 weight part; and |
| water (W) | 85-100 parts by weight. |
Typically, the compound oral liquid preparation comprises:
| components | Dosage of |
| Dextromethorphan hydrobromide | 0.25 to 0.35 part by weight |
| Guaiacol glyceryl ether | 1.5-2.5 parts by weight |
| Sucralose | 0.08-0.12 weight part |
| Ethanol | 3.8 to 4.2 parts by weight of |
| Glycerol | 5.5 to 6.5 parts by weight of |
| Sorbitol | 7 to 9 portions of |
| Xylitol, its preparation method and use | 7 to 9 parts by weight of |
| Fructose | 11 to 13 parts by weight of |
| Hydroxyethyl cellulose | 0.3 to 0.5 part by weight |
| Glycine | 0.2-0.4 weight parts; and |
| water (I) | 85 to 95 weight portions. |
Typically, the compound oral liquid preparation comprises:
typically, the compound oral liquid preparation comprises:
| components | Dosage of |
| Dextromethorphan hydrobromide | 0.3g |
| Guaiacol glyceryl ether | 2.0g |
| Sucralose | 0.1g |
| Ethanol | 4.0g |
| Glycerol | 6.0g |
| Sorbitol | 8.0g |
| Xylitol, its preparation method and use | 8.0g |
| Fructose | 12.0g |
| Hydroxyethyl cellulose | 0.4g |
| Glycine | 0.3g |
| Water (W) | To 100ml. |
The invention also provides a method for preparing the compound oral liquid preparation, which comprises the following steps:
mixing dextromethorphan hydrobromide, guaifenesin, a flavoring agent, a stabilizing agent and a solvent to obtain the compound oral liquid preparation.
Specifically, the preparation method of the compound oral liquid preparation is as described in the second aspect of the invention.
Medicine box
The invention provides a medicine box which comprises a transparent container and the compound oral liquid preparation.
The compound oral liquid preparation can be subpackaged in the transparent container.
The transparent container of the present invention may be a transparent plastic container (e.g., a transparent PET bottle) or a transparent glass container.
The main advantages of the present invention include:
1. compared with the existing liquid preparation subpackaged in the brown container on the market, the compound oral liquid preparation subpackaged in the transparent container not only reduces the production and storage cost, but also is beneficial to the simple, rapid and effective observation of the properties of the compound oral liquid preparation, such as clarity, whether precipitated particles exist, mildew, discoloration, foreign matters, gas generation and other deterioration phenomena, by the transparent container when a patient buys or takes the compound oral liquid preparation, and the safety of taking the compound oral liquid preparation is improved. The compound oral liquid preparation has excellent thermal stability and is convenient to store and transport, so that the storage and transport cost is reduced.
2. The compound oral liquid preparation can cover the bitter taste and residual bitter taste of dextromethorphan hydrobromide and guaifenesin, thereby obviously improving the mouth feel of the compound oral liquid preparation and improving the oral compliance of patients, particularly children.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental methods in the following examples, which are not specified under specific conditions, are generally performed under conventional conditions.
EXAMPLE 1 Compound oral solution
The prescription of the compound oral solution of this example 1 is shown in table 1:
TABLE 1 prescription composition of compound oral solution (specification: 3mg/ml dextromethorphan hydrobromide; 20mg/ml guaifenesin)
The preparation method of the compound oral solution of the embodiment 1 is as follows:
adding ethanol and glycerol into 80% of purified water according to the prescription amount, stirring and mixing, adding dextromethorphan hydrobromide and guaiacol glyceryl ether, stirring and mixing at 50 ℃, adding hydroxyethyl cellulose, stirring and mixing at 50 ℃, then adding sucralose, sorbitol, xylitol, fructose and glycine, stirring and mixing at 50 ℃, adding the rest purified water according to the prescription amount to a dosage volume, filtering through a 0.22 mu m microporous membrane to obtain a compound oral solution, and subpackaging in transparent PET bottles.
Example 2 Compound oral solution
The prescription of the compound oral solution of this example 2 is shown in table 2:
TABLE 2 prescription composition of compound oral solution (specification: dextromethorphan hydrobromide 3mg/ml; guaiacol glyceryl ether 20 mg/ml)
| Components | Amount of the composition |
| Dextromethorphan hydrobromide | 0.3g |
| Guaiacol glyceryl ether | 2.0g |
| Sucralose | 0.1g |
| Ethanol | 4.0g |
| Glycerol | 6.0g |
| Sorbitol | 8.0g |
| Xylitol, its preparation method and use | 8.0g |
| Fructose | 12.0g |
| Purified water | To 100ml. |
The preparation method of the compound oral solution of the embodiment 2 is as follows:
adding ethanol and glycerol into 80% of purified water according to the prescription amount, stirring and mixing, adding dextromethorphan hydrobromide and guaiacol glyceryl ether, stirring and mixing at 50 ℃, then adding sucralose, sorbitol, xylitol and fructose, stirring and mixing at 50 ℃, adding the rest purified water according to the prescription amount to a fixed volume, filtering through a 0.22 mu m microporous filter membrane to obtain a compound oral solution, and subpackaging in transparent PET bottles.
Example 3 Compound oral solution
The prescription of the compound oral solution of this example 3 is shown in table 3:
TABLE 3 prescription composition of compound oral solution (specification: 3mg/ml dextromethorphan hydrobromide; 20mg/ml guaifenesin)
| Components | Dosage of |
| Dextromethorphan hydrobromide | 0.3g |
| Guaifenesin | 2.0g |
| Sucralose | 0.1g |
| Ethanol | 4.0g |
| Glycerol | 6.0g |
| Sorbitol | 8.0g |
| Xylitol, its preparation method and use | 8.0g |
| Hydroxyethyl cellulose | 0.4g |
| Glycine | 0.3g |
| Purified water | To 100ml. |
The preparation method of the compound oral solution of the embodiment 3 is as follows:
adding ethanol and glycerol into 80% of the formula amount of purified water, stirring and mixing, adding dextromethorphan hydrobromide and guaiacol glyceryl ether, stirring and mixing at 50 ℃, adding hydroxyethyl cellulose, stirring and mixing at 50 ℃, then adding sucralose, sorbitol, xylitol and glycine, stirring and mixing at 50 ℃, adding the rest formula amount of purified water to a dosage volume, filtering through a 0.22 mu m microporous membrane to obtain a compound oral solution, and subpackaging in transparent PET bottles.
EXAMPLE 4 Compound oral solution
The prescription of the compound oral solution of this example 4 is shown in table 4:
TABLE 4 prescription composition of compound oral solution (specification: 3mg/ml dextromethorphan hydrobromide; 20mg/ml guaifenesin)
| Components | Dosage of |
| Dextromethorphan hydrobromide | 0.3g |
| Guaiacol glyceryl ether | 2.0g |
| Sucralose | 0.1g |
| Ethanol | 4.0g |
| Glycerol | 6.0g |
| Sorbitol | 8.0g |
| Fructose | 12.0g |
| Hydroxyethyl cellulose | 0.4g |
| Glycine | 0.3g |
| Purified water | To 100ml. |
The preparation method of the compound oral solution of the embodiment 4 is as follows:
adding ethanol and glycerol into 80% of purified water according to the formula amount, stirring and mixing, adding dextromethorphan hydrobromide and guaiacol glyceryl ether, stirring and mixing at 50 ℃, adding hydroxyethyl cellulose, stirring and mixing at 50 ℃, then adding sucralose, sorbitol, fructose and glycine, stirring and mixing at 50 ℃, adding the rest of purified water according to the formula amount to a dosage volume, filtering through a 0.22 mu m microporous filter membrane to obtain a compound oral solution, and subpackaging in transparent PET bottles.
EXAMPLE 5 Compound oral solution
The prescription of the compound oral solution of this example 5 is shown in table 5:
TABLE 5 prescription composition of Compound oral solution (specification: 3mg/ml dextromethorphan hydrobromide; 20mg/ml guaifenesin)
| Components | Dosage of |
| Dextromethorphan hydrobromide | 0.3g |
| Guaiacol glyceryl ether | 2.0g |
| Sucralose | 0.1g |
| Ethanol | 4.0g |
| Glycerol | 6.0g |
| Sorbitol | 8.0g |
| Xylitol, its preparation method and use | 10.0g |
| Fructose | 4.0g |
| Hydroxyethyl cellulose | 0.4g |
| Glycine | 0.3g |
| Purified water | To 100ml. |
The preparation method of the compound oral solution of the embodiment 5 is as follows:
adding ethanol and glycerol into 80% of purified water according to the prescription amount, stirring and mixing, adding dextromethorphan hydrobromide and guaiacol glyceryl ether, stirring and mixing at 50 ℃, adding hydroxyethyl cellulose, stirring and mixing at 50 ℃, then adding sucralose, sorbitol, xylitol, fructose and glycine, stirring and mixing at 50 ℃, adding the rest purified water according to the prescription amount to a dosage volume, filtering through a 0.22 mu m microporous membrane to obtain a compound oral solution, and subpackaging in transparent PET bottles.
Example 6 Compound oral solution
The prescription of the compound oral solution of this example 6 is shown in table 6:
TABLE 6 prescription composition of compound oral solution (specification: dextromethorphan hydrobromide 3mg/ml; guaiacol glyceryl ether 20 mg/ml)
| Components | Amount of the composition |
| Dextromethorphan hydrobromide | 0.3g |
| Guaifenesin | 2.0g |
| Sucralose | 0.1g |
| Ethanol | 4.0g |
| Glycerol | 6.0g |
| Sorbitol | 8.0g |
| Hydroxyethyl cellulose | 0.4g |
| Glycine | 0.3g |
| Purified water | To 100ml. |
The preparation method of the compound oral solution of the present example 6 is as follows:
adding ethanol and glycerol into 80% of purified water according to the formula amount, stirring and mixing, adding dextromethorphan hydrobromide and guaiacol glyceryl ether, stirring and mixing at 50 ℃, adding hydroxyethyl cellulose, stirring and mixing at 50 ℃, then adding sucralose, sorbitol and glycine, stirring and mixing at 50 ℃, adding the rest of purified water according to the formula amount to a dosage volume, filtering through a 0.22 mu m microporous filter membrane to obtain a compound oral solution, and subpackaging in transparent PET bottles.
Example 7 Compound oral solution
The prescription of the compound oral solution of this example 7 is shown in table 7:
TABLE 7 prescription composition of compound oral solution (specification: 3mg/ml dextromethorphan hydrobromide; 20mg/ml guaifenesin)
| Components | Dosage of |
| Dextromethorphan hydrobromide | 0.3g |
| Guaiacol glyceryl ether | 2.0g |
| Sucralose | 0.1g |
| Ethanol | 4.0g |
| Glycerol | 6.0g |
| Sorbitol | 8.0g |
| Xylitol, its preparation method and use | 8.0g |
| Maltitol | 12.0g |
| Hydroxyethyl cellulose | 0.4g |
| Glycine | 0.3g |
| Purified water | To 100ml. |
The preparation method of the compound oral solution of this example 7 is as follows:
adding ethanol and glycerol into 80% of purified water according to the prescription amount, stirring and mixing, adding dextromethorphan hydrobromide and guaiacol glyceryl ether, stirring and mixing at 50 ℃, adding hydroxyethyl cellulose, stirring and mixing at 50 ℃, then adding sucralose, sorbitol, xylitol, maltitol and glycine, stirring and mixing at 50 ℃, adding the rest purified water according to the prescription amount to a dosage volume, filtering through a 0.22 mu m microporous membrane to obtain a compound oral solution, and subpackaging in transparent PET bottles.
Formulation investigation
1. Taste investigation
20 healthy subjects were taken to examine the taste of the compound oral solution prepared in the examples 1 to 7, respectively, and the taste examination indexes include bitterness in the mouth and bitterness residue, and the scoring criteria of each index are as follows: 0 point (none, pleasant mouthfeel); 1 point (slight, not affecting mouthfeel); 2 points (some affect the taste); score 3 (more severe, still acceptable) and score 4 (severe, not acceptable). The test adopts a single blind method, the test subject cannot judge the possible taste of the oral solution to be tasted from the mark or appearance of the compound oral solution, and the investigation result is shown in table 8:
table 8 taste evaluation test results of the compound oral solutions prepared in examples 1 to 7 (n = 20)
| Examples | Bitterness in mouth | Bitter residue |
| Example 1 | 0.4 | 0.3 |
| Example 2 | 2.2 | 2.4 |
| Example 3 | 2.3 | 2.5 |
| Example 4 | 1.8 | 2.1 |
| Example 5 | 2.1 | 2.3 |
| Example 6 | 2.7 | 2.9 |
| Example 7 | 1.9 | 2.1 |
As can be seen from table 8, the compound oral solution prepared in example 1 can significantly improve and mask the bitter taste and residual bitter taste of dextromethorphan hydrobromide and guaifenesin, thereby significantly improving the taste of the compound oral solution and improving oral compliance.
2. Stability study of illumination factors
Referring to the guidelines of the stability test of the formulation in Chinese pharmacopoeia, the stability of the compound oral solution prepared in examples 1-2 packed in transparent PET bottles was examined in a single factor by light under the condition of light (4500 lx,25 ℃) for 0 day, 10 days, 20 days and 30 days after the preparation, and the contents (%) of dextromethorphan hydrobromide and guaiacol glyceryl ether and the contents (%) of impurities were measured by HPLC (high performance liquid chromatography).
The results of the light factor examination of the compound oral solution prepared in example 1-2 dispensed in transparent PET bottles are shown in table 9:
table 9 light factor stability test results for the compound oral solutions prepared in examples 1-2
Remarking: "-" indicates no measurement is required.
As can be seen from table 9, the compound oral solution prepared in example 1 has excellent light stability, and can be simply stored and transported in transparent containers without being stored and transported in brown containers.
3. Accelerated stability review
Referring to the guidelines of the stability test in the chinese pharmacopoeia, the stability of the compound oral solution prepared in example 1 (packaged in transparent PET bottles and packaged in commercially available cartons) after preparation (0 day), accelerated 1, 3 and 6 months was examined by performing accelerated stability test at 40 ± 2 ℃ and 75 ± 5% relative humidity, and determining dextromethorphan hydrobromide and guaiacol glyceryl ether content (%) and impurity content (%) by HPLC (high performance liquid chromatography).
The results of accelerated stability studies of the compound oral solution are shown in table 10:
TABLE 10 accelerated stability test results of the compound oral solution prepared in example 1 at 40 + -2 deg.C and 75 + -5% RH
As can be seen from table 10, the compound oral solution prepared in example 1 has excellent accelerated stability, meets the quality requirements, and thus has excellent storage stability.
While the invention has been described in terms of a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the spirit and scope of the invention.
Claims (5)
1. The compound oral liquid preparation is characterized by comprising the following components:
2. the compound oral liquid preparation of claim 1, which consists of the following components:
3. the compound oral liquid preparation of claim 1, which consists of the following components:
4. a kit comprising a transparent container and the combination oral liquid formulation of claim 1;
the compound oral liquid preparation is respectively packaged in the transparent container.
5. The use of the compound oral liquid preparation of claim 1 for preparing a medicament for preventing upper respiratory tract infection, cough and expectoration caused by bronchitis.
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