CN115025041A - Levocetirizine hydrochloride oral solution - Google Patents
Levocetirizine hydrochloride oral solution Download PDFInfo
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Abstract
The invention relates to a levocetirizine hydrochloride oral solution. The levocetirizine hydrochloride liquid preparation comprises levocetirizine hydrochloride, sucralose, lactose, xylitol, sorbitol, sodium chloride, polyethylene glycol 400, sodium dihydrogen phosphate, disodium hydrogen phosphate and water. The levocetirizine hydrochloride oral solution has excellent mouthfeel and stability.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to levocetirizine hydrochloride oral solution.
Background
Levocetirizine hydrochloride (CAS number: 130018-87-0) is a selective histamine H1 receptor antagonist preparation, is mainly used for relieving allergic symptoms of allergic diseases, is clinically used for treating skin mucosa allergic diseases such as allergic rhinitis, urticaria, angioneurotic edema and the like, and is also used for relieving the allergic symptoms during cold.
Compared with other levocetirizine hydrochloride preparations, the levocetirizine hydrochloride preparation oral solution has the advantages of convenient taking, quick response and the like, and particularly has high oral compliance to the levocetirizine hydrochloride preparation oral solution for patients with swallowing difficulty such as old people or children, so the levocetirizine hydrochloride preparation oral solution has excellent clinical application value.
The existing levocetirizine hydrochloride oral solution still has a plurality of defects, the levocetirizine hydrochloride has strong bitter taste, so that the levocetirizine hydrochloride oral solution has poor taste, although the bitter taste of the oral solution can be reduced by adding sweet taste or aroma to a certain extent through adding a sweetening agent or essence, the bitter taste is difficult to effectively improve, the oral compliance of patients, particularly children, is low, and the essence has a toxic action and is not beneficial to the health of human bodies, so the bitter taste of the levocetirizine hydrochloride oral solution is difficult to improve by the existing technology. The prior levocetirizine hydrochloride oral solution needs to be subpackaged in a brown bottle, so that the degradation of the levocetirizine hydrochloride caused by illumination to avoid content reduction and impurity exceeding is avoided, and the levocetirizine hydrochloride oral solution needs to be preserved in a dark place, however, the subpackaging of the levocetirizine hydrochloride oral solution in the brown bottle and the preservation in the dark place not only increase the production cost and the storage cost, but also are not beneficial to a patient to observe the properties of the levocetirizine hydrochloride oral solution in the bottle, when the patient purchases and takes the levocetirizine hydrochloride oral solution, the properties of the levocetirizine hydrochloride oral solution in the bottle, such as the clarity, whether precipitated particles exist or not, mildew exists, rancidity, discoloration, foreign matters, gas generation and other deterioration phenomena, are difficult to be simply and quickly and effectively observed through the brown bottle, therefore, the patient is difficult to observe and judge the safety of the levocetirizine hydrochloride oral solution when taking the medicine, easily causes the problem of medication safety. In addition, the existing levocetirizine hydrochloride oral solution has low thermal stability, and increases the production and storage cost.
Therefore, there is a need in the art to develop a levocetirizine hydrochloride oral solution having excellent taste and stability, and to improve the oral administration and safety of the levocetirizine hydrochloride oral solution.
Disclosure of Invention
The invention aims to provide a levocetirizine hydrochloride liquid preparation with excellent mouthfeel and stability.
The invention provides a levocetirizine hydrochloride liquid preparation in a first aspect, which comprises levocetirizine hydrochloride, sucralose, lactose, xylitol, sorbitol, sodium chloride, polyethylene glycol 400, sodium dihydrogen phosphate, disodium hydrogen phosphate and water.
Preferably, the levocetirizine hydrochloride liquid preparation is a levocetirizine hydrochloride liquid oral liquid preparation.
Preferably, the levocetirizine hydrochloride liquid preparation is a levocetirizine hydrochloride liquid oral solution.
Preferably, the levocetirizine hydrochloride is present in an amount of 0.1-3mg/ml, preferably 0.1-1mg/ml, more preferably 0.3-0.7mg/ml, more preferably 0.4-0.6mg/ml, most preferably 0.5 mg/ml.
Preferably, the levocetirizine hydrochloride is 0.1 to 3 parts by weight, preferably 0.1 to 1 part by weight, more preferably 0.3 to 0.7 part by weight, more preferably 0.4 to 0.6 part by weight, most preferably 0.5 part by weight.
Preferably, the sucralose is present in an amount of 0.2 to 2mg/ml, preferably 0.3 to 1.2mg/ml, more preferably 0.5 to 1.0mg/ml, more preferably 0.7 to 0.9mg/ml, and most preferably 0.8 mg/ml.
Preferably, the sucralose is 0.2 to 2 parts by weight, preferably 0.3 to 1.2 parts by weight, more preferably 0.5 to 1.0 part by weight, more preferably 0.7 to 0.9 part by weight, and most preferably 0.8 part by weight.
Preferably, the lactose is present in an amount of 25-55mg/ml, preferably 30-50mg/ml, more preferably 35-45mg/ml, more preferably 38-42mg/ml, most preferably 40 mg/ml.
Preferably, the lactose is present in an amount of 25 to 55 parts by weight, preferably 30 to 50 parts by weight, more preferably 35 to 45 parts by weight, more preferably 38 to 42 parts by weight, most preferably 40 parts by weight.
Preferably, the xylitol content is from 5 to 35mg/ml, preferably from 10 to 30mg/ml, more preferably from 15 to 25mg/ml, more preferably from 18 to 22mg/ml, most preferably 20 mg/ml.
Preferably, the xylitol is present in an amount of 5 to 35 parts by weight, preferably 10 to 30 parts by weight, more preferably 15 to 25 parts by weight, still more preferably 18 to 22 parts by weight, most preferably 20 parts by weight.
Preferably, the sorbitol is present in an amount of 15-45mg/ml, preferably 20-40mg/ml, more preferably 25-35mg/ml, more preferably 28-32mg/ml, most preferably 30 mg/ml.
Preferably, the sorbitol is 15 to 45 parts by weight, preferably 20 to 40 parts by weight, more preferably 25 to 35 parts by weight, more preferably 28 to 32 parts by weight, most preferably 30 parts by weight.
Preferably, the sodium chloride is present in an amount of 1-10mg/ml, preferably 2-8mg/ml, more preferably 3-7mg/ml, more preferably 4-6mg/ml, most preferably 5 mg/ml.
Preferably, the sodium chloride is present in an amount of 1 to 10 parts by weight, preferably 2 to 8 parts by weight, more preferably 3 to 7 parts by weight, more preferably 4 to 6 parts by weight, most preferably 5 parts by weight.
Preferably, the polyethylene glycol 400 is present in an amount of 5-25mg/ml, preferably 10-25mg/ml, more preferably 10-20mg/ml, more preferably 13-17mg/ml, most preferably 15 mg/ml.
Preferably, the polyethylene glycol 400 is 5 to 25 parts by weight, preferably 10 to 25 parts by weight, more preferably 10 to 20 parts by weight, still more preferably 13 to 17 parts by weight, and most preferably 15 parts by weight.
Preferably, the content of said sodium dihydrogen phosphate is 0.5-5mg/ml, preferably 1-3mg/ml, more preferably 1.5-2.5mg/ml, more preferably 1.8-2.2mg/ml, most preferably 2 mg/ml.
Preferably, the sodium dihydrogen phosphate is 0.5 to 5 parts by weight, preferably 1 to 3 parts by weight, more preferably 1.5 to 2.5 parts by weight, still more preferably 1.8 to 2.2 parts by weight, most preferably 2 parts by weight.
Preferably, the water content is 800-1200 weight portions, preferably 900-1100 weight portions, more preferably 950-1050 weight portions, more preferably 980-1020 weight portions, and most preferably 1000 weight portions.
Preferably, the liquid levocetirizine hydrochloride formulation has a pH of 3.5 to 5.5, preferably 4.0 to 5.0, more preferably 4.2 to 5.0, more preferably 4.4 to 4.8, more preferably 4.5 to 4.7, most preferably 4.6.
Preferably, the disodium hydrogen phosphate adjusts the pH of the levocetirizine hydrochloride liquid formulation.
Preferably, the water comprises purified water.
Preferably, the levocetirizine hydrochloride liquid preparation comprises:
the levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.2-5.0.
Preferably, the levocetirizine hydrochloride liquid preparation comprises:
| components | Dosage of |
| Levocetirizine hydrochloride | 0.4 to 0.6 part by weight |
| Sucralose | 0.7 to 0.9 part by weight |
| Lactose | 38 to 42 parts by weight of |
| Xylitol, its preparation method and application | 18 to 22 portions of |
| Sorbitol | 28-32 parts by weight |
| Sodium chloride | 4 to 6 parts by weight of |
| Polyethylene glycol 400 | 13 to 17 parts by weight of |
| Sodium dihydrogen phosphate | 1.8-2.2 parts by weight; and |
| purified water | 980 and 1020 parts by weight |
The levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.4-4.8.
Preferably, the levocetirizine hydrochloride liquid preparation comprises:
| components | Amount of the composition |
| Levocetirizine hydrochloride | 0.5 part by weight |
| Sucralose | 0.8 part by weight |
| Lactose | 40 parts by weight of |
| Xylitol, its preparation method and use | 20 parts by weight of |
| Sorbitol | 30 parts by weight of |
| Sodium chloride | 5 parts by weight of |
| Polyethylene glycol 400 | 15 parts by weight of |
| Sodium dihydrogen phosphate | 2 parts by weight; and |
| purified water | 1000 parts by weight |
The levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.6.
Preferably, the levocetirizine hydrochloride liquid preparation comprises:
| components | Dosage of |
| Levocetirizine hydrochloride | 0.5g |
| Sucralose | 0.8g |
| Lactose | 40g |
| Xylitol, its preparation method and use | 20g |
| Sorbitol | 30g |
| Sodium chloride | 5g |
| Polyethylene glycol 400 | 15g |
| Sodium dihydrogen phosphate (dihydrogen phosphate) | 2g of the total weight of the mixture; and |
| water (W) | To 1000ml |
The levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.6.
Preferably, the unit of parts by weight is g.
Preferably, the levocetirizine hydrochloride liquid preparation is subpackaged in transparent containers.
Preferably, the transparent container comprises a transparent plastic container or a transparent glass container.
Preferably, the transparent container comprises a transparent PET bottle.
Preferably, the preparation method of the levocetirizine hydrochloride liquid preparation comprises the following steps:
stirring, mixing and dissolving 70-80% of water and polyethylene glycol 400 at 40-50 ℃, adding sucralose, lactose, xylitol, sorbitol, sodium chloride and sodium dihydrogen phosphate, stirring, mixing and dissolving at 40-50 ℃, adding levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 40-50 ℃ to obtain a liquid medicine; disodium hydrogen phosphate is added into the liquid medicine to adjust the pH of the liquid medicine to 4.4-4.8, then water is added to a constant volume to a dosage volume, the liquid medicine is stirred and mixed uniformly, and the liquid medicine is filtered to obtain the levocetirizine hydrochloride liquid preparation.
Preferably, the method comprises:
stirring, mixing and dissolving 75% of formula amount of water and polyethylene glycol 400 at 45 ℃, adding sucralose, lactose, xylitol, sorbitol, sodium chloride and sodium dihydrogen phosphate, stirring, mixing and dissolving at 45 ℃, then adding levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 45 ℃ to obtain liquid medicine; adding disodium hydrogen phosphate into the liquid medicine to adjust the pH value of the liquid medicine to 4.6, adding water to a constant volume to a dosage volume, stirring and mixing uniformly, and filtering to obtain the levocetirizine hydrochloride liquid preparation.
Preferably, the filtration is by microfiltration.
Preferably, the size of the filtration pores of the microporous filtration membrane is 0.10 to 1.0. mu.m, preferably 0.10 to 0.5. mu.m, more preferably 0.10 to 0.30. mu.m, still more preferably 0.18 to 0.26. mu.m, still more preferably 0.20 to 0.24. mu.m, and most preferably 0.22. mu.m.
In a second aspect of the present invention, there is provided a method for preparing a levocetirizine hydrochloride liquid formulation according to the first aspect of the present invention, said method comprising the steps of:
and mixing the levocetirizine hydrochloride, the sucralose, the lactose, the xylitol, the sorbitol, the sodium chloride, the polyethylene glycol 400, the sodium dihydrogen phosphate, the disodium hydrogen phosphate and water to obtain the levocetirizine hydrochloride liquid preparation.
Preferably, the method comprises:
stirring, mixing and dissolving 70-80% of water and polyethylene glycol 400 at 40-50 ℃, adding sucralose, lactose, xylitol, sorbitol, sodium chloride and sodium dihydrogen phosphate, stirring, mixing and dissolving at 40-50 ℃, adding levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 40-50 ℃ to obtain liquid medicine; adding disodium hydrogen phosphate into the liquid medicine to adjust the pH value of the liquid medicine to 4.4-4.8, adding water to a constant volume to a dosage volume, stirring and mixing uniformly, and filtering to obtain the levocetirizine hydrochloride liquid preparation.
Preferably, the method comprises the following steps:
stirring, mixing and dissolving 75% of water and polyethylene glycol 400 according to the formula amount at 45 ℃, adding sucralose, lactose, xylitol, sorbitol, sodium chloride and sodium dihydrogen phosphate, stirring, mixing and dissolving at 45 ℃, then adding levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 45 ℃ to obtain a liquid medicine; adding disodium hydrogen phosphate into the liquid medicine to adjust the pH value of the liquid medicine to 4.6, adding water to a constant volume to a dosage volume, stirring and mixing uniformly, and filtering to obtain the levocetirizine hydrochloride liquid preparation.
Preferably, the filtration is by microfiltration.
Preferably, the size of the filtration pores of the microporous filtration membrane is 0.10 to 1.0. mu.m, preferably 0.10 to 0.5. mu.m, more preferably 0.10 to 0.30. mu.m, still more preferably 0.18 to 0.26. mu.m, still more preferably 0.20 to 0.24. mu.m, and most preferably 0.22. mu.m.
In a third aspect of the invention, there is provided a kit comprising a transparent container and a liquid formulation of levocetirizine hydrochloride according to the first aspect of the invention.
Preferably, said liquid formulation of levocetirizine hydrochloride according to the first aspect of the present invention is dispensed in said transparent container.
Preferably, the transparent container comprises a transparent plastic container or a transparent glass container.
Preferably, the transparent container comprises a transparent PET bottle.
In a fourth aspect of the present invention, there is provided a use of the levocetirizine hydrochloride liquid preparation according to the first aspect of the present invention for preparing a medicament for alleviating allergic symptoms of allergic diseases.
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 levocetirizine hydrochloride liquid preparation which comprises levocetirizine hydrochloride, sucralose, lactose, xylitol, sorbitol, sodium chloride, polyethylene glycol 400, sodium dihydrogen phosphate, disodium hydrogen phosphate and water.
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 … …", "consisting essentially of … …".
As used herein, the term "PET" refers to polyethylene terephthalate, known by the english name poly (ethylene terephthalate).
As used herein, the term "polyethylene glycol 400" is abbreviated PEG-400, and is known by the English name Poly (ethylene glycol) 400.
As used herein, the terms "levocetirizine hydrochloride" and "levocetirizine hydrochloride" are used interchangeably.
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 levocetirizine hydrochloride liquid preparation, the percentage content of a certain component is (the weight part of the component/the sum of all the weight parts) multiplied by 100 percent, so that in a composition consisting of 1 weight part of the component a and 9 weight parts of the component b, the content of the component a is 10 percent, and the content of the component b is 90 percent.
Liquid preparation
The invention provides a levocetirizine hydrochloride liquid preparation with excellent mouthfeel and stability.
In a preferred embodiment of the present invention, the levocetirizine hydrochloride liquid preparation comprises levocetirizine hydrochloride, sucralose, lactose, xylitol, sorbitol, sodium chloride, polyethylene glycol 400, sodium dihydrogen phosphate, disodium hydrogen phosphate and water.
The levocetirizine hydrochloride liquid preparation is preferably an oral solution.
In a preferred embodiment of the invention, the levocetirizine hydrochloride is present in an amount of 0.1-3mg/ml, preferably 0.1-1mg/ml, more preferably 0.3-0.7mg/ml, more preferably 0.4-0.6mg/ml, most preferably 0.5 mg/ml.
Preferably, the levocetirizine hydrochloride is 0.1 to 3 parts by weight, preferably 0.1 to 1 part by weight, more preferably 0.3 to 0.7 part by weight, more preferably 0.4 to 0.6 part by weight, most preferably 0.5 part by weight.
In a preferred embodiment of the invention, the sucralose is present in an amount of 0.2-2mg/ml, preferably 0.3-1.2mg/ml, more preferably 0.5-1.0mg/ml, more preferably 0.7-0.9mg/ml, and most preferably 0.8 mg/ml.
Preferably, the sucralose is 0.2 to 2 parts by weight, preferably 0.3 to 1.2 parts by weight, more preferably 0.5 to 1.0 part by weight, more preferably 0.7 to 0.9 part by weight, and most preferably 0.8 part by weight.
In a preferred embodiment of the invention, the lactose is present in an amount of 25-55mg/ml, preferably 30-50mg/ml, more preferably 35-45mg/ml, more preferably 38-42mg/ml, most preferably 40 mg/ml.
Preferably, the lactose is present in an amount of 25 to 55 parts by weight, preferably 30 to 50 parts by weight, more preferably 35 to 45 parts by weight, more preferably 38 to 42 parts by weight, most preferably 40 parts by weight.
In a preferred embodiment of the invention, the xylitol is present in an amount of 5-35mg/ml, preferably 10-30mg/ml, more preferably 15-25mg/ml, more preferably 18-22mg/ml, most preferably 20 mg/ml.
Preferably, the xylitol is present in an amount of 5 to 35 parts by weight, preferably 10 to 30 parts by weight, more preferably 15 to 25 parts by weight, still more preferably 18 to 22 parts by weight, most preferably 20 parts by weight.
In a preferred embodiment of the invention, the sorbitol is present in an amount of 15-45mg/ml, preferably 20-40mg/ml, more preferably 25-35mg/ml, more preferably 28-32mg/ml, most preferably 30 mg/ml.
Preferably, the sorbitol is 15 to 45 parts by weight, preferably 20 to 40 parts by weight, more preferably 25 to 35 parts by weight, more preferably 28 to 32 parts by weight, most preferably 30 parts by weight.
In a preferred embodiment of the invention, the sodium chloride is present in an amount of 1-10mg/ml, preferably 2-8mg/ml, more preferably 3-7mg/ml, more preferably 4-6mg/ml, most preferably 5 mg/ml.
Preferably, the sodium chloride is present in an amount of 1 to 10 parts by weight, preferably 2 to 8 parts by weight, more preferably 3 to 7 parts by weight, more preferably 4 to 6 parts by weight, most preferably 5 parts by weight.
In a preferred embodiment of the present invention, the content of the polyethylene glycol 400 is 5-25mg/ml, preferably 10-25mg/ml, more preferably 10-20mg/ml, more preferably 13-17mg/ml, and most preferably 15 mg/ml.
Preferably, the polyethylene glycol 400 is 5 to 25 parts by weight, preferably 10 to 25 parts by weight, more preferably 10 to 20 parts by weight, still more preferably 13 to 17 parts by weight, and most preferably 15 parts by weight.
In a preferred embodiment of the present invention, the content of the sodium dihydrogen phosphate is 0.5-5mg/ml, preferably 1-3mg/ml, more preferably 1.5-2.5mg/ml, more preferably 1.8-2.2mg/ml, and most preferably 2 mg/ml.
Preferably, the sodium dihydrogen phosphate is 0.5 to 5 parts by weight, preferably 1 to 3 parts by weight, more preferably 1.5 to 2.5 parts by weight, still more preferably 1.8 to 2.2 parts by weight, most preferably 2 parts by weight.
In a preferred embodiment of the present invention, the water content is 800-.
In a preferred embodiment of the present invention, the pH of the levocetirizine hydrochloride liquid preparation is 3.5-5.5, preferably 4.0-5.0, more preferably 4.2-5.0, more preferably 4.4-4.8, more preferably 4.5-4.7, most preferably 4.6.
Preferably, the disodium hydrogen phosphate adjusts the pH of the levocetirizine hydrochloride liquid formulation.
Preferably, the water comprises purified water.
Typically, the levocetirizine hydrochloride liquid preparation comprises:
| components | Amount of the composition |
| Levocetirizine hydrochloride | 0.3 to 0.7 part by weight |
| Sucralose | 0.5 to 1.0 part by weight |
| Lactose | 35 to 45 parts by weight of |
| Xylitol, its preparation method and use | 15-25 parts by weight |
| Sorbitol | 25-35 parts by weight |
| Sodium chloride | 3 to 7 parts by weight of |
| Polyethylene glycol 400 | 10-20 parts by weight |
| Sodium dihydrogen phosphate | 1.5-2.5 weight parts; and |
| purified water | 950 + 1050 parts by weight |
The levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.2-5.0.
Typically, the levocetirizine hydrochloride liquid preparation comprises:
the levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.4-4.8.
Typically, the levocetirizine hydrochloride liquid preparation comprises:
| components | Dosage of |
| Levocetirizine hydrochloride | 0.5 part by weight |
| Sucralose | 0.8 part by weight |
| Lactose | 40 parts by weight of |
| Xylitol, its preparation method and use | 20 parts by weight of |
| Sorbitol | 30 parts by weight of |
| Sodium chloride | 5 parts by weight of |
| Polyethylene glycol 400 | 15 parts by weight of |
| Sodium dihydrogen phosphate | 2 parts by weight; and |
| purified water | 1000 parts by weight |
The levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.6.
Typically, the levocetirizine hydrochloride liquid formulation comprises:
| components | Dosage of |
| Levocetirizine hydrochloride | 0.5g |
| Sucralose | 0.8g |
| Lactose | 40g |
| Xylitol, its preparation method and use | 20g |
| Sorbitol | 30g |
| Sodium chloride | 5g |
| Polyethylene glycol 400 | 15g |
| Sodium dihydrogen phosphate | 2g of the total weight of the mixture; and |
| water (W) | To 1000ml |
The levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.6.
The levocetirizine hydrochloride liquid preparation can be subpackaged in transparent containers, for example, the transparent containers comprise transparent plastic (such as PET) containers or transparent glass containers.
Method
The invention provides a preparation method of a levocetirizine hydrochloride liquid preparation, which comprises the following steps:
and mixing the levocetirizine hydrochloride, the sucralose, the lactose, the xylitol, the sorbitol, the sodium chloride, the polyethylene glycol 400, the sodium dihydrogen phosphate, the disodium hydrogen phosphate and water to obtain the levocetirizine hydrochloride liquid preparation.
In a preferred embodiment of the present invention, the method comprises:
stirring, mixing and dissolving 70-80% of water and polyethylene glycol 400 at 40-50 ℃, adding sucralose, lactose, xylitol, sorbitol, sodium chloride and sodium dihydrogen phosphate, stirring, mixing and dissolving at 40-50 ℃, adding levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 40-50 ℃ to obtain a liquid medicine; disodium hydrogen phosphate is added into the liquid medicine to adjust the pH of the liquid medicine to 4.4-4.8, then water is added to a constant volume to a dosage volume, the liquid medicine is stirred and mixed uniformly, and the liquid medicine is filtered to obtain the levocetirizine hydrochloride liquid preparation.
In a preferred embodiment of the present invention, the method comprises:
stirring, mixing and dissolving 75% of water and polyethylene glycol 400 according to the formula amount at 45 ℃, adding sucralose, lactose, xylitol, sorbitol, sodium chloride and sodium dihydrogen phosphate, stirring, mixing and dissolving at 45 ℃, then adding levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 45 ℃ to obtain a liquid medicine; adding disodium hydrogen phosphate into the liquid medicine to adjust the pH value of the liquid medicine to 4.6, adding water to a constant volume to a dosage volume, stirring and mixing uniformly, and filtering to obtain the levocetirizine hydrochloride liquid preparation.
Preferably, the filtration is by microfiltration.
Preferably, the size of the filtration pore of the microporous filtration membrane is 0.10 to 1.0. mu.m, preferably 0.10 to 0.5. mu.m, more preferably 0.10 to 0.30. mu.m, still more preferably 0.18 to 0.26. mu.m, still more preferably 0.20 to 0.24. mu.m, and most preferably 0.22. mu.m.
Medicine box
The invention also provides a kit which comprises a transparent container and the levocetirizine hydrochloride liquid preparation.
In a preferred embodiment of the present invention, the levocetirizine hydrochloride liquid preparation is separately packaged in the transparent container.
The transparent container according to the present invention may comprise a transparent plastic container or a transparent glass container. For example, the transparent container comprises a transparent PET bottle.
Use of
The invention also provides a levocetirizine hydrochloride liquid preparation for preparing a medicine for relieving the allergic symptoms of allergic diseases.
The main excellent technical effects of the invention comprise:
1. the levocetirizine hydrochloride liquid preparation can effectively improve the bitter taste, thereby obviously improving the oral compliance of patients such as children.
2. The levocetirizine hydrochloride liquid preparation has excellent light stability, can be simply subpackaged in a transparent container for storage and transportation, does not need to be subpackaged in a brown container for storage and transportation, reduces the production and storage cost, can be used for quickly and simply observing the properties of the levocetirizine hydrochloride oral solution, such as clarity, whether precipitated particles exist, whether mildew exists, rancidity, discoloration, foreign matters, gas generation and other deterioration phenomena, through the transparent container when a patient buys and takes the levocetirizine hydrochloride oral solution, and effectively ensures the medication safety of the levocetirizine hydrochloride oral solution
3. The levocetirizine hydrochloride oral solution has excellent thermal stability and is convenient to store and transport.
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 Levocetirizine hydrochloride oral solution
The formula of the levocetirizine hydrochloride oral solution of this example 1 is shown in table 1:
TABLE 1 prescription composition of levocetirizine hydrochloride oral solution (specification: 0.5mg/ml)
| Components | Dosage of |
| Levocetirizine hydrochloride | 0.5g |
| Sucralose | 0.8g |
| Lactose | 40g |
| Xylitol, its preparation method and use | 20g |
| Sorbitol | 30g |
| Sodium chloride | 5g |
| Polyethylene glycol 400 | 15g |
| Sodium dihydrogen phosphate | 2g |
| Disodium hydrogen phosphate | Proper amount of |
| Purified water | To 1000ml |
The preparation method of the levocetirizine hydrochloride oral solution of the embodiment 1 is as follows:
after boiling and cooling 75% of the prescription amount of purified water and the prescription amount of polyethylene glycol 400, stirring, mixing and dissolving at 45 ℃, adding the prescription amount of sucralose, the prescription amount of lactose, the prescription amount of xylitol, the prescription amount of sorbitol, the prescription amount of sodium chloride and the prescription amount of sodium dihydrogen phosphate, stirring, mixing and dissolving at 45 ℃, then adding the prescription amount of levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 45 ℃ to obtain a liquid medicine; adding 10 wt% of disodium hydrogen phosphate aqueous solution into the liquid medicine to adjust the pH value of the liquid medicine to 4.6, adding boiled and cooled purified water to a constant volume to a dosage volume, stirring and mixing uniformly, filtering by a 0.22 mu m microporous filter membrane to obtain levocetirizine hydrochloride oral solution, and subpackaging in transparent PET bottles, wherein the specification of each bottle of levocetirizine hydrochloride is 0.5 mg/ml.
Comparative example 1 levocetirizine hydrochloride oral solution
The formulation of the levocetirizine hydrochloride oral solution of this comparative example 1 is shown in table 2:
TABLE 2 prescription composition of levocetirizine hydrochloride oral solution (specification: 0.5mg/ml)
| Components | Dosage of |
| Levocetirizine hydrochloride | 0.5g |
| Sucralose | 0.8g |
| Lactose | 40g |
| Xylitol, its preparation method and use | 20g |
| Sodium chloride | 5g |
| Sodium dihydrogen phosphate | 2g |
| Disodium hydrogen phosphate | Proper amount of |
| Purified water | To 1000ml |
The preparation method of the levocetirizine hydrochloride oral solution of the comparative example 1 is as follows:
stirring, mixing and dissolving 75% of purified water according to the prescription amount, sucralose according to the prescription amount, lactose according to the prescription amount, xylitol according to the prescription amount, sodium chloride according to the prescription amount and sodium dihydrogen phosphate according to the prescription amount after boiling and cooling at 45 ℃, then adding levocetirizine hydrochloride according to the prescription amount, and continuously stirring, mixing and dissolving at 45 ℃ to obtain a liquid medicine; adding 10 wt% of disodium hydrogen phosphate aqueous solution into the liquid medicine to adjust the pH value of the liquid medicine to 4.6, adding boiled and cooled purified water to a constant volume to a dosage volume, stirring and mixing uniformly, filtering by a 0.22 mu m microporous filter membrane to obtain levocetirizine hydrochloride oral solution, and subpackaging in transparent PET bottles, wherein the specification of each bottle of levocetirizine hydrochloride is 0.5 mg/ml.
Comparative example 2 levocetirizine hydrochloride oral solution
The formulation of the levocetirizine hydrochloride oral solution of this comparative example 2 is shown in table 3:
TABLE 3 prescription composition of levocetirizine hydrochloride oral solution (specification: 0.5mg/ml)
| Components | Amount of the composition |
| Levocetirizine hydrochloride | 0.5g |
| Sucralose | 0.8g |
| Lactose | 40g |
| Xylitol, its preparation method and use | 20g |
| Sorbitol | 30g |
| Sodium chloride | 5g |
| Sodium dihydrogen phosphate (dihydrogen phosphate) | 2g |
| Disodium hydrogen phosphate | Proper amount of |
| Purified water | To 1000ml |
The preparation method of the levocetirizine hydrochloride oral solution of the comparative example 2 is as follows:
stirring, mixing and dissolving 75% of purified water in a prescription amount, sucralose in a prescription amount, lactose in a prescription amount, xylitol in a prescription amount, sorbitol in a prescription amount, sodium chloride in a prescription amount and sodium dihydrogen phosphate in a prescription amount at 45 ℃, adding levocetirizine hydrochloride in a prescription amount, and continuously stirring, mixing and dissolving at 45 ℃ to obtain a liquid medicine; adding 10 wt% of disodium hydrogen phosphate aqueous solution into the liquid medicine to adjust the pH value of the liquid medicine to 4.6, adding boiled and cooled purified water to a constant volume to a dosage volume, stirring and mixing uniformly, filtering by a 0.22 mu m microporous filter membrane to obtain levocetirizine hydrochloride oral solution, and subpackaging in transparent PET bottles, wherein the specification of each bottle of levocetirizine hydrochloride is 0.5 mg/ml.
Comparative example 3 levocetirizine hydrochloride oral solution
The formulation of the levocetirizine hydrochloride oral solution of this comparative example 3 is shown in table 4:
TABLE 4 prescription composition of levocetirizine hydrochloride oral solution (specification: 0.5mg/ml)
The preparation method of the levocetirizine hydrochloride oral solution of the comparative example 3 is as follows:
after boiling and cooling 75% of the prescription amount of purified water and the prescription amount of polyethylene glycol 400, stirring, mixing and dissolving at 45 ℃, adding the prescription amount of sucralose, the prescription amount of lactose, the prescription amount of xylitol, the prescription amount of sodium chloride and the prescription amount of sodium dihydrogen phosphate, stirring, mixing and dissolving at 45 ℃, then adding the prescription amount of levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 45 ℃ to obtain a liquid medicine; the pH value of the liquid medicine is adjusted to 4.6 by adding 10 wt% of disodium hydrogen phosphate aqueous solution into the liquid medicine, then adding boiled and cooled purified water to a constant volume to a dosage volume, stirring and mixing uniformly, filtering through a 0.22 mu m microporous membrane to obtain levocetirizine hydrochloride oral solution, and subpackaging in transparent PET bottles, wherein the specification of each bottle of levocetirizine hydrochloride is 0.5 mg/ml.
Comparative example 4 levocetirizine hydrochloride oral solution
The formulation of the levocetirizine hydrochloride oral solution of this comparative example 4 is shown in table 5:
TABLE 5 prescription composition of levocetirizine hydrochloride oral solution (specification: 0.5mg/ml)
| Components | Dosage of |
| Levocetirizine hydrochloride | 0.5g |
| Sucralose | 0.8g |
| Lactose | 40g |
| Xylitol, its preparation method and use | 20g |
| Sorbitol | 10g |
| Sodium chloride | 5g |
| Polyethylene glycol 400 | 30g |
| Sodium dihydrogen phosphate | 2g |
| Disodium hydrogen phosphate | Proper amount of |
| Purified water | To 1000ml |
The preparation method of the levocetirizine hydrochloride oral solution of the comparative example 4 is as follows:
after boiling and cooling 75% of the prescription amount of purified water and the prescription amount of polyethylene glycol 400, stirring, mixing and dissolving at 45 ℃, adding the prescription amount of sucralose, the prescription amount of lactose, the prescription amount of xylitol, the prescription amount of sorbitol, the prescription amount of sodium chloride and the prescription amount of sodium dihydrogen phosphate, stirring, mixing and dissolving at 45 ℃, then adding the prescription amount of levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 45 ℃ to obtain a liquid medicine; adding 10 wt% of disodium hydrogen phosphate aqueous solution into the liquid medicine to adjust the pH value of the liquid medicine to 4.6, adding boiled and cooled purified water to a constant volume to a dosage volume, stirring and mixing uniformly, filtering by a 0.22 mu m microporous filter membrane to obtain levocetirizine hydrochloride oral solution, and subpackaging in transparent PET bottles, wherein the specification of each bottle of levocetirizine hydrochloride is 0.5 mg/ml.
Comparative example 5 levocetirizine hydrochloride oral solution
The formulation of the levocetirizine hydrochloride oral solution of this comparative example 5 is shown in table 6:
TABLE 6 prescription composition of levocetirizine hydrochloride oral solution (specification: 0.5mg/ml)
| Components | Amount of the composition |
| Levocetirizine hydrochloride | 0.5g |
| Sucralose | 0.8g |
| Lactose | 50g |
| Xylitol, its preparation method and use | 20g |
| Sorbitol | 10g |
| Sodium chloride | 5g |
| Polyethylene glycol 400 | 15g |
| Sodium dihydrogen phosphate (dihydrogen phosphate) | 2g |
| Disodium hydrogen phosphate | Proper amount of |
| Purified water | To 1000ml |
The preparation method of the levocetirizine hydrochloride oral solution of the comparative example 5 is as follows:
after boiling and cooling 75% of the prescription amount of purified water and the prescription amount of polyethylene glycol 400, stirring, mixing and dissolving at 45 ℃, adding the prescription amount of sucralose, the prescription amount of lactose, the prescription amount of xylitol, the prescription amount of sorbitol, the prescription amount of sodium chloride and the prescription amount of sodium dihydrogen phosphate, stirring, mixing and dissolving at 45 ℃, then adding the prescription amount of levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 45 ℃ to obtain a liquid medicine; adding 10 wt% of disodium hydrogen phosphate aqueous solution into the liquid medicine to adjust the pH value of the liquid medicine to 4.6, adding boiled and cooled purified water to a constant volume to a dosage volume, stirring and mixing uniformly, filtering by a 0.22 mu m microporous filter membrane to obtain levocetirizine hydrochloride oral solution, and subpackaging in transparent PET bottles, wherein the specification of each bottle of levocetirizine hydrochloride is 0.5 mg/ml.
Comparative example 6 levocetirizine hydrochloride oral solution
The formulation of the levocetirizine hydrochloride oral solution of this comparative example 6 is shown in table 7:
TABLE 7 prescription composition of levocetirizine hydrochloride oral solution (specification: 0.5mg/ml)
The preparation method of the levocetirizine hydrochloride oral solution of the comparative example 6 is as follows:
stirring, mixing and dissolving 75% of purified water and polyethylene glycol 400 at 45 ℃ after boiling and cooling, adding sucralose, fructose, xylitol, sorbitol, sodium chloride and sodium dihydrogen phosphate at 45 ℃, stirring, mixing and dissolving, adding levocetirizine hydrochloride at 45 ℃, and continuously stirring, mixing and dissolving to obtain a liquid medicine; adding 10 wt% of disodium hydrogen phosphate aqueous solution into the liquid medicine to adjust the pH value of the liquid medicine to 4.6, adding boiled and cooled purified water to a constant volume to a dosage volume, stirring and mixing uniformly, filtering by a 0.22 mu m microporous filter membrane to obtain levocetirizine hydrochloride oral solution, and subpackaging in transparent PET bottles, wherein the specification of each bottle of levocetirizine hydrochloride is 0.5 mg/ml.
The taste and stability of levocetirizine hydrochloride oral solutions prepared in example 1 of the present invention and comparative examples 1 to 6 were examined
1. Evaluation of mouthfeel
The evaluation method is as follows: 20 healthy subjects were taken and oral observations of the oral levocetirizine hydrochloride solutions prepared in example 1 of the present invention and comparative examples 1 to 6 were made.
The taste evaluation index is the degree of bitterness in the mouth, and the scoring standard is 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 (strong, not acceptable).
In the test of taste evaluation, the subject was unable to make a possible taste judgment in advance of the oral solution to be tasted from the oral solution labeling and appearance using a single blind method.
The taste evaluation results of the levocetirizine hydrochloride oral solutions prepared in example 1 and comparative examples 1 to 6 are shown in the following table 8:
table 8 taste evaluation of levocetirizine hydrochloride oral solutions prepared in example 1 and comparative examples 1 to 6
| Experimental group | Bitterness in mouth |
| Example 1 | 0.4 |
| Comparative example 1 | 2.6 |
| Comparative example 2 | 1.5 |
| Comparative example 3 | 2.1 |
| Comparative example 4 | 1.8 |
| Comparative example 5 | 1.5 |
| Comparative example 6 | 1.1 |
As seen from table 8, the compound oral solution prepared in the examples has significantly excellent mouthfeel, can effectively improve and mask the bitter taste of levocetirizine hydrochloride, and thus has excellent mouthfeel and oral compliance.
2. Stability study of illumination factors
The levocetirizine hydrochloride oral solution prepared in the embodiment 1 and the comparative examples 1 to 6 of the invention is respectively packaged in a transparent PET bottle, then the transparent PET bottle packaged with the levocetirizine hydrochloride oral solution is placed under the illumination condition (4500lx, 25 ℃) for 0 day (after preparation), 10 days, 20 days and 30 days, and the illumination stability of the levocetirizine hydrochloride oral solution packaged in the transparent PET bottle is examined according to the guidance principle of Chinese pharmacopoeia preparation stability test.
The stability inspection indexes of the illumination factors are as follows: the content (%) of the levocetirizine hydrochloride and the content (%) of total impurities of the levocetirizine hydrochloride oral solution subpackaged in transparent PET bottles at different investigation time points under the illumination condition are measured by HPLC (high performance liquid chromatography), wherein the limit of the content of the levocetirizine hydrochloride is 90-110%, and the limit of the total impurities is less than or equal to 0.8%.
The results of the light factor examination of the levocetirizine hydrochloride oral solutions prepared in example 1 and comparative examples 1 to 6 dispensed in transparent PET bottles at different examination time points are shown in table 9:
table 9 levocetirizine hydrochloride oral soluble light factor stability test prepared in example 1 and comparative examples 1-6 (n ═ 6)
As can be seen from table 9, the levocetirizine hydrochloride oral solution prepared in example 1 has excellent light stability, can be simply and separately packaged in a transparent container for storage and transportation, and does not need to be separately packaged in a brown container for storage and transportation, so that the production and storage costs are reduced, and when a patient purchases and takes the levocetirizine hydrochloride oral solution, the patient can simply and quickly observe the characteristics of the levocetirizine hydrochloride oral solution, such as clarity, whether precipitated particles exist, mildew, rancidity, discoloration, foreign matters, gas generation and other deterioration phenomena, through the transparent container, so that the medication safety of the levocetirizine hydrochloride oral solution is effectively ensured.
3. Accelerated stability review
The levocetirizine hydrochloride oral solution prepared in the embodiment 1 of the invention is respectively packaged in transparent PET bottles and packaged by cartons on the market, then the levocetirizine hydrochloride oral solution (respectively packaged in the transparent PET bottles and packaged by cartons on the market) is placed for 0 day (after preparation), 1 month, 3 months and 6 months under the conditions that the temperature is 40 +/-2 ℃ and the relative humidity is RH75 +/-5 percent, and the accelerated stability of the levocetirizine hydrochloride oral solution which is respectively packaged in the transparent PET bottles and packaged by cartons on the market is examined according to the Chinese pharmacopoeia preparation stability test guiding principle.
Accelerated stability survey index: the content (%) of levocetirizine hydrochloride and the content (%) of total impurities of levocetirizine hydrochloride oral solutions (subpackaged in transparent PET bottles and packaged by cartons on the market) at different investigation time points under accelerated conditions (40 +/-2 ℃ and RH75 +/-5%) are determined by HPLC (high performance liquid chromatography), wherein the limit of the content of levocetirizine hydrochloride is 90-110%, and the limit of the total impurities is less than or equal to 0.8%.
The results of accelerated stability studies of levocetirizine hydrochloride oral solutions prepared in example 1, dispensed in clear PET bottles and packaged in commercial cartons, at different investigation time points are shown in table 10:
table 10 accelerated stability test of levocetirizine hydrochloride oral solutions prepared in example 1 at 40 ± 2 ℃ and RH75 ± 5% (n ═ 6)
It can be seen from table 10 that the levocetirizine hydrochloride oral solution prepared in example 1 has excellent accelerated stability, thereby having excellent storage and transportation 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 (10)
1. The levocetirizine hydrochloride liquid preparation is characterized by comprising levocetirizine hydrochloride, sucralose, lactose, xylitol, sorbitol, sodium chloride, polyethylene glycol 400, sodium dihydrogen phosphate, disodium hydrogen phosphate and water.
2. The levocetirizine hydrochloride liquid preparation of claim 1, wherein the levocetirizine hydrochloride liquid preparation is a levocetirizine hydrochloride liquid oral solution.
3. The levocetirizine hydrochloride liquid formulation of claim 1, wherein the levocetirizine hydrochloride is in the range of 0.1 to 3 parts by weight, preferably 0.1 to 1 part by weight, more preferably 0.3 to 0.7 part by weight, more preferably 0.4 to 0.6 part by weight, most preferably 0.5 part by weight;
the sucralose is 0.2 to 2 parts by weight, preferably 0.3 to 1.2 parts by weight, more preferably 0.5 to 1.0 part by weight, more preferably 0.7 to 0.9 part by weight, and most preferably 0.8 part by weight;
the lactose is 25-55 parts by weight, preferably 30-50 parts by weight, more preferably 35-45 parts by weight, more preferably 38-42 parts by weight, most preferably 40 parts by weight;
the xylitol is 5 to 35 parts by weight, preferably 10 to 30 parts by weight, more preferably 15 to 25 parts by weight, more preferably 18 to 22 parts by weight, and most preferably 20 parts by weight;
the sorbitol is 15 to 45 parts by weight, preferably 20 to 40 parts by weight, more preferably 25 to 35 parts by weight, more preferably 28 to 32 parts by weight, and most preferably 30 parts by weight;
the sodium chloride is 1 to 10 parts by weight, preferably 2 to 8 parts by weight, more preferably 3 to 7 parts by weight, more preferably 4 to 6 parts by weight, most preferably 5 parts by weight;
the polyethylene glycol 400 is 5 to 25 parts by weight, preferably 10 to 25 parts by weight, more preferably 10 to 20 parts by weight, more preferably 13 to 17 parts by weight, and most preferably 15 parts by weight;
the sodium dihydrogen phosphate is 0.5-5 parts by weight, preferably 1-3 parts by weight, more preferably 1.5-2.5 parts by weight, more preferably 1.8-2.2 parts by weight, most preferably 2 parts by weight; and/or
The water content is 800-.
4. The levocetirizine hydrochloride liquid formulation of claim 1, wherein the pH of the levocetirizine hydrochloride liquid formulation is 3.5 to 5.5, preferably 4.0 to 5.0, more preferably 4.2 to 5.0, more preferably 4.4 to 4.8, more preferably 4.5 to 4.7, most preferably 4.6.
5. The levocetirizine hydrochloride liquid formulation of claim 1, wherein the levocetirizine hydrochloride liquid formulation comprises:
The levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.2-5.0.
6. The levocetirizine hydrochloride liquid formulation of claim 1, wherein the levocetirizine hydrochloride liquid formulation comprises:
The levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.4-4.8.
7. The levocetirizine hydrochloride liquid formulation of claim 1, wherein the levocetirizine hydrochloride liquid formulation comprises:
the levocetirizine hydrochloride liquid preparation also comprises disodium hydrogen phosphate, and the pH value of the levocetirizine hydrochloride liquid preparation is 4.6.
8. The levocetirizine hydrochloride liquid preparation of claim 1, wherein the preparation method of the levocetirizine hydrochloride liquid preparation comprises:
stirring, mixing and dissolving 70-80% of water and polyethylene glycol 400 at 40-50 ℃, adding sucralose, lactose, xylitol, sorbitol, sodium chloride and sodium dihydrogen phosphate, stirring, mixing and dissolving at 40-50 ℃, adding levocetirizine hydrochloride, and continuously stirring, mixing and dissolving at 40-50 ℃ to obtain a liquid medicine; adding disodium hydrogen phosphate into the liquid medicine to adjust the pH value of the liquid medicine to 4.4-4.8, adding water to a constant volume to a dosage volume, stirring and mixing uniformly, and filtering to obtain the levocetirizine hydrochloride liquid preparation.
9. A kit comprising a transparent container and the levocetirizine hydrochloride liquid formulation of claim 1;
the levocetirizine hydrochloride liquid preparation of claim 1 is separately packaged in the transparent container.
10. Use of the levocetirizine hydrochloride liquid formulation according to claim 1 for the preparation of a medicament for alleviating the allergic symptoms of allergic diseases.
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| US20030118654A1 (en) * | 2001-12-07 | 2003-06-26 | B. Santos Joyce Bedelia | Taste masked aqueous liquid pharmaceutical composition |
| CN102133179A (en) * | 2011-03-11 | 2011-07-27 | 重庆健能医药开发有限公司 | Stable cetirizine oral solution |
| CN103463089A (en) * | 2013-08-26 | 2013-12-25 | 王大光 | Cetirizine hydrochloride oral solution and preparation method thereof |
| CN106491522A (en) * | 2016-09-24 | 2017-03-15 | 北京万全德众医药生物技术有限公司 | A kind of levo-cetirizine hydrochloride Oral drops and preparation method thereof |
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|---|---|---|---|---|
| US20030118654A1 (en) * | 2001-12-07 | 2003-06-26 | B. Santos Joyce Bedelia | Taste masked aqueous liquid pharmaceutical composition |
| CN102133179A (en) * | 2011-03-11 | 2011-07-27 | 重庆健能医药开发有限公司 | Stable cetirizine oral solution |
| CN103463089A (en) * | 2013-08-26 | 2013-12-25 | 王大光 | Cetirizine hydrochloride oral solution and preparation method thereof |
| CN106491522A (en) * | 2016-09-24 | 2017-03-15 | 北京万全德众医药生物技术有限公司 | A kind of levo-cetirizine hydrochloride Oral drops and preparation method thereof |
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