A levetiracetam oral solution

Abstract

The present application relates to a levetiracetam oral solution. Specifically, the present application provides a levetiracetam oral solution comprising levetiracetam, sucralose, polyethylene glycol 400, glycerol, lactose, mannitol, sorbitol, hydroxyethyl cellulose, citric acid, disodium hydrogen phosphate, sodium bisulfite and water. The levetiracetam oral solution of the present application can effectively mask the bitter taste of levetiracetam and its residues, thereby having excellent oral compliance, and the levetiracetam oral solution has excellent stability to light, high temperature and high humidity, can be divided and packed in transparent containers, is convenient for storage and transportation, ensures quality safety, and guarantees medication safety.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparations, and more specifically to a levetiracetam oral solution. Background Technology

[0002] Levetiracetam (CAS No.: 102767-28-2) is an antiepileptic drug primarily used as adjunctive therapy for partial seizures in adults and children aged 4 years and older with epilepsy. The structural formula of levetiracetam is as follows:

[0003]

[0004] Levetiracetam is commonly available in clinical formulations including tablets, injections, and oral solutions. While oral solutions offer convenience, rapid onset of action, and high patient compliance, their strong bitter taste and lingering bitterness, coupled with the need for long-term administration, lead to poor compliance, especially in children. Furthermore, levetiracetam exhibits poor stability under light and high temperature / humidity conditions, necessitating storage in light-protected brown bottles. This brown-bottled packaging makes it difficult for patients to easily and quickly assess the oral solution's properties, such as clarity, presence of sediment, mold, or foreign matter, increasing medication safety concerns. Additionally, brown-bottled packaging increases production costs.

[0005] Therefore, there is a need in this field to develop a levetiracetam oral solution that improves the taste and stability of the levetiracetam oral solution, thereby enhancing its application value. Summary of the Invention

[0006] The purpose of this invention is to provide a levetiracetam oral solution that has an excellent taste, improves patient compliance, and also has excellent stability.

[0007] In a first aspect, the present invention provides a levetiracetam oral solution comprising levetiracetam, sucralose, polyethylene glycol 400, glycerin, lactose, mannitol, sorbitol, hydroxyethyl cellulose, citric acid, disodium hydrogen phosphate, sodium bisulfite, and water.

[0008] Preferably, the levetiracetam is 5-15 parts by weight, more preferably 8-12 parts by weight, and even more preferably 10 parts by weight.

[0009] Preferably, the content of levetiracetam is 5-15g / 100ml, more preferably 8-12g / 100ml, and even more preferably 10g / 100ml.

[0010] Preferably, the sucralose is 0.05-0.15 parts by weight, more preferably 0.06-0.10 parts by weight, and even more preferably 0.08 parts by weight.

[0011] Preferably, the content of sucralose is 0.05-0.15g / 100ml, more preferably 0.06-0.10g / 100ml, and even more preferably 0.08g / 100ml.

[0012] Preferably, the polyethylene glycol 400 is 0.5-1.5 parts by weight, more preferably 0.8-1.2 parts by weight, and even more preferably 1.0 parts by weight.

[0013] Preferably, the content of polyethylene glycol 400 is 0.5-1.5g / 100ml, more preferably 0.8-1.2g / 100ml, and even more preferably 1.0g / 100ml.

[0014] Preferably, the glycerol is 2.0-3.0 parts by weight, more preferably 2.3-2.7 parts by weight, and even more preferably 2.5 parts by weight.

[0015] Preferably, the glycerol content is 2.0-3.0g / 100ml, more preferably 2.3-2.7g / 100ml, and even more preferably 2.5g / 100ml.

[0016] Preferably, the lactose is 0.2-0.8 parts by weight, more preferably 0.4-0.6 parts by weight, and even more preferably 0.5 parts by weight.

[0017] Preferably, the lactose content is 0.2-0.8g / 100ml, more preferably 0.4-0.6g / 100ml, and even more preferably 0.5g / 100ml.

[0018] Preferably, the mannitol is 1.0-2.0 parts by weight, more preferably 1.3-1.7 parts by weight, and even more preferably 1.5 parts by weight.

[0019] Preferably, the mannitol content is 1.0-2.0g / 100ml, more preferably 1.3-1.7g / 100ml, and even more preferably 1.5g / 100ml.

[0020] Preferably, the sorbitol is 1.5-2.5 parts by weight, more preferably 1.8-2.2 parts by weight, and even more preferably 2.0 parts by weight.

[0021] Preferably, the sorbitol content is 1.5-2.5g / 100ml, more preferably 1.8-2.2g / 100ml, and even more preferably 2.0g / 100ml.

[0022] Preferably, the hydroxyethyl cellulose is 0.2-1.0 parts by weight, more preferably 0.4-0.8 parts by weight, and even more preferably 0.6 parts by weight.

[0023] Preferably, the content of hydroxyethyl cellulose is 0.2-1.0 g / 100 ml, more preferably 0.4-0.8 g / 100 ml, and even more preferably 0.6 g / 100 ml.

[0024] Preferably, the citric acid is 0.02-0.08 parts by weight, more preferably 0.03-0.07 parts by weight, and even more preferably 0.05 parts by weight.

[0025] Preferably, the citric acid content is 0.02-0.08 g / 100 ml, more preferably 0.03-0.07 g / 100 ml, and even more preferably 0.05 g / 100 ml.

[0026] Preferably, the disodium hydrogen phosphate is 0.1-0.5 parts by weight, more preferably 0.2-0.4 parts by weight, and even more preferably 0.3 parts by weight.

[0027] Preferably, the content of disodium hydrogen phosphate is 0.1-0.5g / 100ml, more preferably 0.2-0.4g / 100ml, and even more preferably 0.3g / 100ml.

[0028] Preferably, the sodium bisulfite is 0.02-0.06 parts by weight, more preferably 0.03-0.05 parts by weight, and even more preferably 0.04 parts by weight.

[0029] Preferably, the sodium bisulfite content is 0.02-0.06 g / 100 ml, more preferably 0.03-0.05 g / 100 ml, and even more preferably 0.04 g / 100 ml.

[0030] Preferably, the water is 90-110 parts by weight, more preferably 95-105 parts by weight, and even more preferably 100 parts by weight.

[0031] Preferably, the water is purified water.

[0032] Preferably, the levetiracetam oral solution comprises:

[0033] Components Dosage Levetiracetam 5-15 parts by weight Sucralose 0.05-0.15 parts by weight Polyethylene glycol 400 0.5-1.5 parts by weight glycerin 2.0-3.0 parts by weight lactose 0.2-0.8 parts by weight Mannitol 1.0-2.0 parts by weight Sorbitol 1.5-2.5 parts by weight Hydroxyethyl cellulose 0.3-1.0 parts by weight Citric acid 0.02-0.08 parts by weight disodium hydrogen phosphate 0.1-0.5 parts by weight Sodium bisulfite 0.02-0.06 parts by weight; and water 90-110 parts by weight.

[0034] Preferably, the levetiracetam oral solution comprises:

[0035] Components Dosage levetiracetam 8-12 parts by weight Sucralose 0.06-0.10 parts by weight Polyethylene glycol 400 0.8-1.2 parts by weight glycerin 2.3-2.7 parts by weight lactose 0.4-0.6 parts by weight Mannitol 1.3-1.7 parts by weight Sorbitol 1.8-2.2 parts by weight Hydroxyethyl cellulose 0.5-0.7 parts by weight Citric acid 0.04-0.06 parts by weight disodium hydrogen phosphate 0.2-0.4 parts by weight Sodium bisulfite 0.03-0.05 parts by weight; and water 95-105 parts by weight.

[0036] Preferably, the levetiracetam oral solution comprises:

[0037]

[0038]

[0039] Preferably, the levetiracetam oral solution comprises:

[0040] Components Dosage Levetiracetam 10g Sucralose 0.08g Polyethylene glycol 400 1.0g glycerin 2.5g lactose 0.5g Mannitol 1.5g Sorbitol 2.0g Hydroxyethyl cellulose 0.6g Citric acid 0.05g disodium hydrogen phosphate 0.3g Sodium bisulfite 0.04g; and Add water Up to 100ml.

[0041] In a second aspect, the present invention provides a method for preparing a levetiracetam oral solution as described in the first aspect of the present invention, the method comprising the steps of:

[0042] The levetiracetam oral solution was obtained by mixing levetiracetam, sucralose, polyethylene glycol 400, glycerin, lactose, mannitol, sorbitol, hydroxyethyl cellulose, citric acid, disodium hydrogen phosphate, sodium bisulfite, and water.

[0043] Preferably, the levetiracetam oral solution is prepared by the following method:

[0044] (1) Take 75-85% of the prescribed amount of water after boiling and cooling, add the prescribed amount of hydroxyethyl cellulose, stir and mix at 35-45℃, add the prescribed amount of polyethylene glycol 400 and the prescribed amount of glycerin, stir and mix at 35-45℃, add the prescribed amount of levetiracetam, stir and mix at 35-45℃ to obtain the drug solution.

[0045] (2) Add the prescribed amounts of sucralose, lactose, mannitol, sorbitol, citric acid, disodium hydrogen phosphate, and sodium bisulfite to the drug solution obtained in step (1). After stirring and mixing at 35-45℃, add boiled and cooled water to make up to the drug volume. After stirring and mixing, filter through 0.45μm and 0.22μm microporous membranes to obtain levetiracetam oral solution.

[0046] In a third aspect, the present invention provides a medicine box comprising a transparent container and a levetiracetam oral solution as described in the first aspect of the present invention;

[0047] The levetiracetam oral solution is dispensed into the transparent container.

[0048] Preferably, the transparent container includes a transparent plastic container (such as a transparent PET bottle) or a transparent glass container.

[0049] In a fourth aspect, the present invention provides the use of levetiracetam oral solution as described in the first aspect of the present invention for the preparation of an antiepileptic drug.

[0050] Preferably, the epilepsy includes partial seizure epilepsy.

[0051] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Detailed Implementation

[0052] This invention develops a levetiracetam oral solution that effectively masks the bitterness and residue of levetiracetam, thus exhibiting excellent oral compliance. Furthermore, the levetiracetam oral solution demonstrates excellent stability under light, high temperature, and high humidity conditions, and can be packaged in transparent containers for easy storage and transportation, ensuring quality and safety, and guaranteeing medication safety.

[0053] the term

[0054] As used herein, the terms “comprising,” “including,” and “containing” are used interchangeably and include not only closed definitions but also semi-closed and open definitions. In other words, the terms include “consisting of” and “substantially consisting of”.

[0055] As used in this article, the term "PET" refers to polyethylene terephthalate, also known as polyethylene terephthalate.

[0056] As used herein, the term "parts by weight" can be any fixed weight expressed in milligrams, grams, or kilograms (e.g., 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 pharmaceutical composition described herein, the percentage content of a component = (the number of parts by weight of that component / the sum of the number of parts by weight of all components) × 100%. Therefore, 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] Levetiracetam oral solution and its preparation method

[0058] This invention provides a levetiracetam oral solution, which comprises levetiracetam, sucralose, polyethylene glycol 400, glycerin, lactose, mannitol, sorbitol, hydroxyethyl cellulose, citric acid, disodium hydrogen phosphate, sodium bisulfite, and water.

[0059] In a preferred embodiment of the present invention, the levetiracetam is 5-15 parts by weight, more preferably 8-12 parts by weight, and even more preferably 10 parts by weight.

[0060] Preferably, the content of levetiracetam is 5-15g / 100ml, more preferably 8-12g / 100ml, and even more preferably 10g / 100ml.

[0061] In a preferred embodiment of the present invention, the sucralose is 0.05-0.15 parts by weight, more preferably 0.06-0.10 parts by weight, and even more preferably 0.08 parts by weight.

[0062] Preferably, the content of sucralose is 0.05-0.15g / 100ml, more preferably 0.06-0.10g / 100ml, and even more preferably 0.08g / 100ml.

[0063] In a preferred embodiment of the present invention, the polyethylene glycol 400 is 0.5-1.5 parts by weight, more preferably 0.8-1.2 parts by weight, and even more preferably 1.0 parts by weight.

[0064] Preferably, the content of polyethylene glycol 400 is 0.5-1.5g / 100ml, more preferably 0.8-1.2g / 100ml, and even more preferably 1.0g / 100ml.

[0065] In a preferred embodiment of the present invention, the glycerol is 2.0-3.0 parts by weight, more preferably 2.3-2.7 parts by weight, and even more preferably 2.5 parts by weight.

[0066] Preferably, the glycerol content is 2.0-3.0g / 100ml, more preferably 2.3-2.7g / 100ml, and even more preferably 2.5g / 100ml.

[0067] In a preferred embodiment of the present invention, the lactose is 0.2-0.8 parts by weight, more preferably 0.4-0.6 parts by weight, and even more preferably 0.5 parts by weight.

[0068] Preferably, the lactose content is 0.2-0.8g / 100ml, more preferably 0.4-0.6g / 100ml, and even more preferably 0.5g / 100ml.

[0069] In a preferred embodiment of the present invention, the mannitol is 1.0-2.0 parts by weight, more preferably 1.3-1.7 parts by weight, and even more preferably 1.5 parts by weight.

[0070] Preferably, the mannitol content is 1.0-2.0g / 100ml, more preferably 1.3-1.7g / 100ml, and even more preferably 1.5g / 100ml.

[0071] In a preferred embodiment of the present invention, the sorbitol is 1.5-2.5 parts by weight, more preferably 1.8-2.2 parts by weight, and even more preferably 2.0 parts by weight.

[0072] Preferably, the sorbitol content is 1.5-2.5g / 100ml, more preferably 1.8-2.2g / 100ml, and even more preferably 2.0g / 100ml.

[0073] In a preferred embodiment of the present invention, the hydroxyethyl cellulose is 0.2-1.0 parts by weight, more preferably 0.4-0.8 parts by weight, and even more preferably 0.6 parts by weight.

[0074] Preferably, the content of hydroxyethyl cellulose is 0.2-1.0 g / 100 ml, more preferably 0.4-0.8 g / 100 ml, and even more preferably 0.6 g / 100 ml.

[0075] In a preferred embodiment of the present invention, the citric acid is 0.02-0.08 parts by weight, more preferably 0.03-0.07 parts by weight, and even more preferably 0.05 parts by weight.

[0076] Preferably, the citric acid content is 0.02-0.08 g / 100 ml, more preferably 0.03-0.07 g / 100 ml, and even more preferably 0.05 g / 100 ml.

[0077] In a preferred embodiment of the present invention, the disodium hydrogen phosphate is 0.1-0.5 parts by weight, more preferably 0.2-0.4 parts by weight, and even more preferably 0.3 parts by weight.

[0078] Preferably, the content of disodium hydrogen phosphate is 0.1-0.5g / 100ml, more preferably 0.2-0.4g / 100ml, and even more preferably 0.3g / 100ml.

[0079] In a preferred embodiment of the present invention, the sodium bisulfite is 0.02-0.06 parts by weight, more preferably 0.03-0.05 parts by weight, and even more preferably 0.04 parts by weight.

[0080] Preferably, the sodium bisulfite content is 0.02-0.06 g / 100 ml, more preferably 0.03-0.05 g / 100 ml, and even more preferably 0.04 g / 100 ml.

[0081] In a preferred embodiment of the present invention, the water is 90-110 parts by weight, more preferably 95-105 parts by weight, and even more preferably 100 parts by weight.

[0082] Representatively, the levetiracetam oral solution comprises:

[0083]

[0084]

[0085] Representatively, the levetiracetam oral solution comprises:

[0086] Components Dosage Levetiracetam 8-12 parts by weight Sucralose 0.06-0.10 parts by weight Polyethylene glycol 400 0.8-1.2 parts by weight glycerin 2.3-2.7 parts by weight lactose 0.4-0.6 parts by weight Mannitol 1.3-1.7 parts by weight Sorbitol 1.8-2.2 parts by weight Hydroxyethyl cellulose 0.5-0.7 parts by weight Citric acid 0.04-0.06 parts by weight disodium hydrogen phosphate 0.2-0.4 parts by weight Sodium bisulfite 0.03-0.05 parts by weight; and water 95-105 parts by weight.

[0087] Typically, the levetiracetam oral solution comprises:

[0088] Components Dosage Levetiracetam 10 portions by weight Sucralose 0.08 parts by weight Polyethylene glycol 400 1.0 part by weight glycerin 2.5 parts by weight lactose 0.5 parts by weight Mannitol 1.5 parts by weight Sorbitol 2.0 parts by weight Hydroxyethyl cellulose 0.6 parts by weight Citric acid 0.05 parts by weight disodium hydrogen phosphate 0.3 parts by weight Sodium bisulfite 0.04 parts by weight; and water 95-105 parts by weight.

[0089] Typically, the levetiracetam oral solution comprises:

[0090]

[0091]

[0092] This invention provides a method for preparing the levetiracetam oral solution of this invention, the method comprising the steps of:

[0093] The levetiracetam oral solution was obtained by mixing levetiracetam, sucralose, polyethylene glycol 400, glycerin, lactose, mannitol, sorbitol, hydroxyethyl cellulose, citric acid, disodium hydrogen phosphate, sodium bisulfite, and water.

[0094] Typically, the levetiracetam oral solution is prepared by the following method:

[0095] (1) Take 75-85% of the prescribed amount of water after boiling and cooling, add the prescribed amount of hydroxyethyl cellulose, stir and mix at 35-45℃, add the prescribed amount of polyethylene glycol 400 and the prescribed amount of glycerin, stir and mix at 35-45℃, add the prescribed amount of levetiracetam, stir and mix at 35-45℃ to obtain the drug solution.

[0096] (2) Add the prescribed amounts of sucralose, lactose, mannitol, sorbitol, citric acid, disodium hydrogen phosphate, and sodium bisulfite to the drug solution obtained in step (1). After stirring and mixing at 35-45℃, add boiled and cooled water to make up to the drug volume. After stirring and mixing, filter through 0.45μm and 0.22μm microporous membranes to obtain levetiracetam oral solution.

[0097] use

[0098] The present invention also provides the use of the levetiracetam oral solution described herein in the preparation of an antiepileptic drug.

[0099] Preferably, the epilepsy includes partial seizure epilepsy.

[0100] The main superior technical effects of this invention include:

[0101] This invention develops a levetiracetam oral solution that effectively masks the bitterness and residue of levetiracetam, thus exhibiting excellent oral compliance and making it suitable for patients, especially children. The levetiracetam oral solution of this invention possesses excellent stability under light, high temperature, and high humidity conditions. It can be packaged in transparent containers for storage and transportation. When purchasing or using the levetiracetam oral solution, patients can easily and quickly observe its properties, such as clarity, presence of sediment, mold, foreign matter, and other signs of deterioration, through the transparent container, ensuring medication safety. Furthermore, its high temperature and high humidity stability effectively guarantees the stability of the levetiracetam oral solution during transportation and storage, facilitating storage and transportation and ensuring quality and safety.

[0102] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions.

[0103] Example 1: Levetiracetam Oral Solution

[0104] In Example 1, a levetiracetam oral solution was prepared. The formulation of the levetiracetam oral solution is shown in Table 1.

[0105] Table 1. Prescription composition of levetiracetam oral solution (levetiracetam strength is 0.1g / ml)

[0106] Components Dosage Levetiracetam 10g Sucralose 0.08g Polyethylene glycol 400 1.0g glycerin 2.5g lactose 0.5g Mannitol 1.5g Sorbitol 2.0g Hydroxyethyl cellulose 0.6g Citric acid 0.05g disodium hydrogen phosphate 0.3g Sodium bisulfite 0.04g Add purified water Up to 100ml.

[0107] The preparation method of the levetiracetam oral solution in Example 1 is as follows:

[0108] (1) Take 80% of the prescribed amount of purified water after boiling and cooling, add the prescribed amount of hydroxyethyl cellulose, stir and mix at 40°C, add the prescribed amount of polyethylene glycol 400 and the prescribed amount of glycerin, stir and mix at 40°C, add the prescribed amount of levetiracetam, stir and mix at 40°C to obtain the drug solution.

[0109] (2) Add the prescribed amounts of sucralose, lactose, mannitol, sorbitol, citric acid, disodium hydrogen phosphate, and sodium bisulfite to the drug solution obtained in step (1). After stirring and mixing at 40°C, add boiled and cooled purified water to make up to the drug volume. After stirring and mixing, filter through 0.45μm and 0.22μm microporous membranes to obtain levetiracetam oral solution, which is then dispensed into transparent PET bottles.

[0110] Example 2: Levetiracetam Oral Solution

[0111] In Example 2, a levetiracetam oral solution was prepared. The formulation of the levetiracetam oral solution is shown in Table 2.

[0112] Table 2. Prescription composition of levetiracetam oral solution (levetiracetam specification: 0.1g / ml)

[0113]

[0114]

[0115] The preparation method of the levetiracetam oral solution in Example 2 is as follows:

[0116] (1) Take 80% of the prescribed amount of purified water after boiling and cooling, add the prescribed amount of hydroxyethyl cellulose, stir and mix at 40°C, add the prescribed amount of polyethylene glycol 400 and the prescribed amount of glycerin, stir and mix at 40°C, add the prescribed amount of levetiracetam, stir and mix at 40°C to obtain the drug solution.

[0117] (2) Add the prescribed amounts of sucralose, lactose, mannitol, sorbitol, tartaric acid, disodium hydrogen phosphate, and sodium bisulfite to the drug solution obtained in step (1). After stirring and mixing at 40°C, add boiled and cooled purified water to make up to the drug volume. After stirring and mixing, filter through 0.45μm and 0.22μm microporous membranes in sequence to obtain levetiracetam oral solution, which is then dispensed into transparent PET bottles.

[0118] Example 3: Levetiracetam Oral Solution

[0119] In Example 3, a levetiracetam oral solution was prepared. The formulation of the levetiracetam oral solution is shown in Table 3.

[0120] Table 3. Prescription composition of levetiracetam oral solution (levetiracetam strength is 0.1g / ml)

[0121] Components Dosage Levetiracetam 10g Sucralose 0.08g Polyethylene glycol 400 1.0g glycerin 2.5g lactose 0.5g Sorbitol 2.0g Hydroxyethyl cellulose 0.6g Citric acid 0.05g disodium hydrogen phosphate 0.3g Sodium bisulfite 0.04g Add purified water Up to 100ml.

[0122] The preparation method of the levetiracetam oral solution in Example 3 is as follows:

[0123] (1) Take 80% of the prescribed amount of purified water after boiling and cooling, add the prescribed amount of hydroxyethyl cellulose, stir and mix at 40°C, add the prescribed amount of polyethylene glycol 400 and the prescribed amount of glycerin, stir and mix at 40°C, add the prescribed amount of levetiracetam, stir and mix at 40°C to obtain the drug solution.

[0124] (2) Add the prescribed amounts of sucralose, lactose, sorbitol, citric acid, disodium hydrogen phosphate, and sodium bisulfite to the drug solution obtained in step (1). After stirring and mixing at 40°C, add boiled and cooled purified water to make up to the drug volume. After stirring and mixing, filter through 0.45μm and 0.22μm microporous membranes in sequence to obtain levetiracetam oral solution, which is then dispensed into transparent PET bottles.

[0125] Example 4: Levetiracetam Oral Solution

[0126] In Example 4, a levetiracetam oral solution was prepared. The formulation of the levetiracetam oral solution is shown in Table 4.

[0127] Table 4. Prescription composition of levetiracetam oral solution (levetiracetam strength is 0.1g / ml)

[0128] Components Dosage levetiracetam 10g Sucralose 0.08g Polyethylene glycol 400 1.0g glycerin 0.6g lactose 0.5g Mannitol 1.5g Sorbitol 2.0g Hydroxyethyl cellulose 1.0g Citric acid 0.05g disodium hydrogen phosphate 0.3g Sodium bisulfite 0.04g Add purified water Up to 100ml.

[0129] The preparation method of the levetiracetam oral solution in Example 4 is as follows:

[0130] (1) Take 80% of the prescribed amount of purified water after boiling and cooling, add the prescribed amount of hydroxyethyl cellulose, stir and mix at 40°C, add the prescribed amount of polyethylene glycol 400 and the prescribed amount of glycerin, stir and mix at 40°C, add the prescribed amount of levetiracetam, stir and mix at 40°C to obtain the drug solution.

[0131] (2) Add the prescribed amounts of sucralose, lactose, mannitol, sorbitol, citric acid, disodium hydrogen phosphate, and sodium bisulfite to the drug solution obtained in step (1). After stirring and mixing at 40°C, add boiled and cooled purified water to make up to the drug volume. After stirring and mixing, filter through 0.45μm and 0.22μm microporous membranes to obtain levetiracetam oral solution, which is then dispensed into transparent PET bottles.

[0132] Example 5: Levetiracetam Oral Solution

[0133] Example 5 describes the preparation of a levetiracetam oral solution. The formulation of the levetiracetam oral solution is shown in Table 5.

[0134] Table 5. Prescription composition of levetiracetam oral solution (levetiracetam strength is 0.1g / ml)

[0135]

[0136]

[0137] The preparation method of the levetiracetam oral solution in Example 5 is as follows:

[0138] (1) Take 80% of the prescribed amount of purified water after boiling and cooling, add the prescribed amount of hydroxyethyl cellulose, stir and mix at 40°C, add the prescribed amount of glycerin, stir and mix at 40°C, add the prescribed amount of levetiracetam, stir and mix at 40°C to obtain the drug solution.

[0139] (2) Add the prescribed amounts of sucralose, lactose, mannitol, sorbitol, citric acid, disodium hydrogen phosphate, and sodium bisulfite to the drug solution obtained in step (1). After stirring and mixing at 40°C, add boiled and cooled purified water to make up to the drug volume. After stirring and mixing, filter through 0.45μm and 0.22μm microporous membranes to obtain levetiracetam oral solution, which is then dispensed into transparent PET bottles.

[0140] Taste and stability study of levetiracetam oral solution

[0141] 1. Taste test

[0142] Twenty subjects were given oral administration of the levetiracetam oral solution prepared in Examples 1-5 to evaluate its taste. The taste evaluation index was initial bitterness and bitterness residue. The scoring criteria for initial bitterness and bitterness residue were as follows: 0 points (none, pleasant taste); 1 point (slight, does not affect taste); 2 points (present, affects taste); 3 points (relatively serious, still acceptable); 4 points (serious, unacceptable).

[0143] In the taste evaluation test, a single-blind method was used, and subjects could not make a prior judgment on the possible taste of the levetiracetam oral solution based on the label. The results are shown in Table 6.

[0144] Table 6. Taste evaluation of the levetiracetam oral solutions prepared in Examples 1-5

[0145] experimental group Bitterness upon entry Bitterness lingering Example 1 0.2 0.1 Example 2 0.8 0.5 Example 3 2.8 2.1 Example 4 1.9 1.4 Example 5 2.4 1.8

[0146] As can be seen from Table 6, the levetiracetam oral solution prepared in this embodiment can improve the bitterness of levetiracetam. In particular, the levetiracetam oral solution prepared in Example 1 has an excellent taste and can effectively mask the bitterness and its residue, thus having excellent oral compliance and being suitable for oral administration by patients, especially children.

[0147] 2. Stability investigation of light factors

[0148] The levetiracetam oral solutions prepared in Examples 1-5 and packaged in transparent PET bottles were placed under light conditions (4500 lx, 25°C) for 0, 5, and 10 days. The levetiracetam content, levetiracetam acid impurity content, and total impurity content at different time points were determined by high performance liquid chromatography according to the guidelines for stability testing of Chinese Pharmacopoeia preparations. The light stability of the levetiracetam oral solutions prepared in Examples 1-5 was then investigated. The results are shown in Table 7.

[0149] Table 7. Stability study of levetiracetam oral solutions prepared in Examples 1-5 under light conditions (4500 lx, 25 °C)

[0150]

[0151] As can be seen from Table 7, the levetiracetam oral solution prepared in Example 1 has strong light stability and excellent light stability. It can be dispensed into transparent containers for storage and transportation, which not only reduces production and storage costs, but also allows patients to easily and quickly observe the properties of the levetiracetam oral solution, such as clarity, presence of precipitates, mold, foreign matter, and other signs of deterioration, through the transparent container when purchasing or using it, thus ensuring medication safety.

[0152] 3. Accelerated stability study under high temperature and high humidity

[0153] The levetiracetam oral solution prepared in Example 1, dispensed into transparent PET bottles, was placed at a temperature of 40±2℃ and a relative humidity (RH) of 75±5% for 0 days, 1, 3, and 6 months. Following the guidelines for stability testing of preparations in the Chinese Pharmacopoeia, the levetiracetam content, levetiracetam acid impurity content, and total impurity content at different testing time points were determined by high-performance liquid chromatography (HPLC). This was to investigate the accelerated stability of the levetiracetam oral solution prepared in Example 1 under high temperature and high humidity conditions. The results are shown in Table 8.

[0154] Table 8. Accelerated stability study of the levetiracetam oral solution prepared in Example 1 at a temperature of 40±2℃ and a relative humidity (RH) of 75±5%.

[0155]

[0156] As can be seen from Table 8, the levetiracetam oral solution prepared in Example 1 has excellent high temperature and high humidity stability, which can reduce the storage and transportation costs of levetiracetam oral solution while ensuring the quality requirements of levetiracetam oral solution during transportation and storage, thus ensuring quality and safety.

[0157] The above description is an implementation scheme designed for one case of the present invention. It should be noted that for those skilled in the art, several improvements can be made without departing from the principle of the present invention, and these improvements should also be considered within the scope of protection of the present invention.

Claims

1. A levetiracetam oral solution, characterized in that, The levetiracetam oral solution is composed of the following components:

2. The levetiracetam oral solution as described in claim 1, characterized in that, The levetiracetam oral solution is composed of the following components:

3. A method for preparing the levetiracetam oral solution as described in claim 1, the method comprising the steps of: The levetiracetam oral solution was obtained by mixing levetiracetam, sucralose, polyethylene glycol 400, glycerin, lactose, mannitol, sorbitol, hydroxyethyl cellulose, citric acid, disodium hydrogen phosphate, sodium bisulfite, and water.

4. A medicine box, characterized in that, The medicine box includes a transparent container and the levetiracetam oral solution as described in claim 1; The levetiracetam oral solution is dispensed into the transparent container.

5. The use of the levetiracetam oral solution as described in claim 1, characterized in that, Used in the preparation of antiepileptic drugs.

6. The use as described in claim 5, characterized in that, The epilepsy mentioned includes partial seizure epilepsy.

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