Levocarnitine oral gel and method of preparation thereof

Abstract

This invention belongs to the field of pharmaceutical formulations, specifically relating to a levocarnitine oral gel and its preparation method. This invention discloses a stable levocarnitine oral gel composition comprising levocarnitine, a gel matrix, an alkali metal salt, and sodium polyacrylate. The stable levocarnitine oral gel disclosed in this invention is easy to swallow, has good medication adherence, does not undergo dehydration and shrinkage during the observation period, has stable product quality, good safety, and is convenient to carry and use; the process is simpler, with high production efficiency and lower risk, making it suitable for large-scale industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparations, specifically relating to a levocarnitine oral gel and its preparation method. Background Technology

[0002] L-carnitine is an essential naturally occurring substance in mammals for energy metabolism, its main function being to promote lipid metabolism. During ischemia and hypoxia, acyl-CoA accumulates, as does long-chain acylcarnitine in mitochondria, while free carnitine is significantly depleted. Ischemia and hypoxia lead to decreased ATP levels and increased permeability of cell membranes and subcellular membranes. Accumulated acyl-CoA can cause changes in membrane structure, leading to membrane collapse and cell death. Furthermore, hypoxia primarily results in anaerobic glycolysis of glucose, and the accumulation of fatty acids leads to acidosis, ion imbalance, and cell autolysis. Sufficient free carnitine can allow accumulated acyl-CoA to enter the mitochondria, reducing its inhibition of adenine nucleotide translocases and facilitating oxidative phosphorylation. L-carnitine is a major energy source for muscle cells, especially cardiomyocytes, and many tissues and organs, such as the brain and kidneys, also rely primarily on fatty acid oxidation for energy. Carnitine can also increase the activity of NADH cytochrome reductase and cytochrome oxidase, accelerate ATP production, and participate in the detoxification of certain drugs. For various tissue ischemia and hypoxia, L-carnitine improves the energy supply to tissues and organs by increasing energy production. Other functions of L-carnitine include: oxidation of medium- and long-chain fatty acids; oxidation by fatty acid peroxidase; buffering the ratio of bound to free coenzyme A; generating energy from ketones, pyruvate, and amino acids (including branched-chain amino acids); removing the toxicity of excessive coenzyme A; and regulating blood ammonia concentration.

[0003] Currently available levocarnitine drugs include levocarnitine tablets, oral solutions, and injections, and are approved for use in patients with chronic renal failure undergoing long-term hemodialysis for a range of complications caused by secondary levocarnitine deficiency.

[0004] Chinese patent application 202110203449.8 describes the preparation of L-carnitine tablets using a dry granulation method. Due to L-carnitine's hygroscopic nature, it is formulated as a solid dosage form. However, this method fails to address the issues of demanding production environment requirements (especially relative humidity), stringent production conditions, and difficulty in storage. The L-carnitine tablets are 330mg in strength, with a tablet weight exceeding 500mg, and require a minimum dosage of three tablets at a time, leading to poor patient compliance, particularly among those with swallowing difficulties.

[0005] Chinese patent application 200910015178.2 discloses a levocarnitine oral solution and its preparation method. The formulation contains up to 15% ethanol (w / v), which is detrimental to health, especially in children, and affects driving safety with long-term use. Levocarnitine has poor stability, and liquid formulations are easily affected by external environmental factors such as light and heat. The sterilization process results in a high amount of impurities, particularly an increase in the potentially toxic impurity trimethylamine (TMA). Conventional oral solutions are packaged in glass, which is inconvenient to carry and use.

[0006] The shortcomings of existing technology: Current L-carnitine oral solution formulations contain up to 15% ethanol (w / v), which is detrimental to health, especially in children, and may affect driving safety with long-term use. L-carnitine also has poor stability, and liquid formulations are easily affected by external environmental factors such as light and heat. The sterilization process leads to a higher concentration of impurities, particularly an increased level of the potentially toxic impurity trimethylamine (TMA). Furthermore, conventional oral solution packaging is made of glass, which is inconvenient to carry and use. Currently available L-carnitine tablets are typically manufactured using dry granulation. Due to L-carnitine's hygroscopic nature, producing solid dosage forms, especially chewable tablets, does not address the challenges of demanding production environments (particularly relative humidity), stringent manufacturing conditions, and poor storage. L-carnitine tablets are typically 330mg, with a tablet weight greater than 500mg, and require a minimum of three tablets at a time. Chewable L-carnitine tablets are 1000mg, with a diameter exceeding 16mm, requiring chewing into small pieces before swallowing, which reduces medication adherence in groups with swallowing difficulties, such as children and the elderly. More than 50% of children cannot swallow standard-sized pills or capsules. Patients with swallowing disorders or dysphagia also struggle with solid dosage forms. In adults, the prevalence of dysphagia can be as high as 16%, with over 37% experiencing difficulty swallowing. This may lead patients to skip or modify (e.g., crush) their medication, potentially altering pharmacokinetic characteristics and failing to achieve the desired therapeutic effect. L-carnitine raw material has strong hygroscopicity, and solid dosage forms have high requirements for the environment (especially relative humidity), demanding production conditions and are not easy to store.

[0007] In view of the shortcomings of the existing technology, the inventors hope to improve the shortcomings of existing oral levocarnitine formulations and to invent a levocarnitine drug formulation with high dosing compliance and stability, which combines the advantages of solid and liquid dosage forms.

[0008] Therefore, developing a levocarnitine oral gel that is easy to swallow, has good medication adherence, does not undergo dehydration and shrinkage during the observation period, has stable product quality (trimethylamine TMA impurities are below the control threshold of 0.06%), good safety, is convenient to carry and use, and has a high drug loading capacity, in order to address unmet clinical needs for medication, is of great clinical significance.

[0009] This invention provides a stable, non-dehydrating, and non-shrinking oral gel formulation of L-carnitine. It is a semi-solid jelly, offering high dosing compliance, easy swallowing, a pleasant taste, and the ability to be taken without water. The composition's portability allows for unrestricted administration at any time or place. This invention provides a high-drug-load oral gel with a L-carnitine content greater than 25%, reducing the amount of composition required for a single dose. As an oral gel for pharmaceutical use, the L-carnitine oral gel not only requires an excellent taste to improve dosing compliance but also, unlike jelly foods, requires stability of the active ingredient and formulation functions (such as gel strength and dissolution). Dehydration and shrinkage during stability testing are reduced by using sodium polyacrylate or partially neutralized sodium polyacrylate. It possesses sufficient gel strength so that the composition does not break during transport or before administration, but readily disintegrates and is swallowed once ingested. Furthermore, as an oral gel, it achieves the same in vitro release characteristics and similar gastrointestinal bioavailability as L-carnitine tablets. The method for preparing the composition is easy to operate, does not involve sterilization steps, and keeps the toxic impurity trimethylamine (TMA) below the control threshold, making it suitable for industrial production.

[0010] However, of all the efforts made to date, there is no public information regarding the availability of L-carnitine oral gel, and attempts to develop a stable oral gel containing L-carnitine are virtually unknown to date. Summary of the Invention

[0011] To address the shortcomings of existing technologies, the present invention aims to provide a levocarnitine oral gel and its preparation method. The levocarnitine oral gel of the present invention is convenient to take, has a good taste, overcomes the difficulty of administration for elderly patients and patients with swallowing difficulties, and improves medication adherence; the process is simpler, has high production efficiency and low risk, and is suitable for large-scale industrial production.

[0012] The main technical features of this invention are: The L-carnitine oral gel contains L-carnitine, a gel matrix, an alkali metal salt, and sodium polyacrylate; The content of levocarnitine is 25-50% of the total weight of the composition; The gel matrix is ​​selected from at least one of carrageenan, pectin, and xanthan gum, and its content accounts for 0.3-5% of the total weight of the composition; The alkali metal salt is selected from at least one of sodium chloride, potassium chloride, sodium citrate, calcium citrate, and calcium lactate, and its content accounts for 0.1-3% of the total weight of the composition; The sodium polyacrylate is selected from fully neutralized sodium polyacrylate or partially neutralized sodium polyacrylate; The sodium polyacrylate content accounts for 0.005-0.25% of the total weight of the composition; The oral gel also contains 0.5-10% by weight of a humectant selected from at least one of glycerin and propylene glycol; It also contains 0.05-5% by weight of a pH adjuster selected from at least one of citric acid, malic acid, fumaric acid, sorbic acid, and glacial acetic acid. It also contains 2.5-25% by weight of a sweetener, selected from at least one of sugars and / or sugar alcohols; It also contains 0.01-5% of a preservative by weight of the total composition, selected from at least one of methylparaben, ethylparaben, propylparaben, potassium sorbate, and sodium benzoate; It also contains 0.01-1.5% of a flavoring agent by weight of the total composition, selected from at least one of banana flavoring, pineapple flavoring, vanillin, strawberry flavoring, orange flavoring, and apple flavoring; The oral gel was tested at 40°C and 75% relative humidity for 6 months and did not undergo dehydration or shrinkage. The oral gel composition has a gel strength of 50-250 gf / cm. 2 Between 140-210 gf / cm³, preferably 140-210 gf / cm³ 2 between; The non-sterile preparation method of the L-carnitine oral gel includes the following steps: heating an appropriate amount of purified water, adding gel matrix and sodium polyacrylate in sequence and stirring to disperse and dissolve them, cooling down and adding L-carnitine to dissolve it, adding alkali metal salt and other components, and stirring evenly; dispensing into a predetermined plastic packaging container, sealing it and allowing it to cool naturally to obtain the oral gel. The non-sterile preparation method of the L-carnitine oral gel further includes the following steps: heating an appropriate amount of purified water to 80-85°C, adding the gel matrix and sodium polyacrylate in sequence and stirring to disperse and dissolve them, cooling to 30-45°C and then adding L-carnitine to dissolve it, adding alkali metal salts and other components, and stirring evenly; dispensing into predetermined plastic packaging containers, sealing and allowing them to cool naturally to obtain the oral gel.

[0013] The beneficial effects of this invention are: 1. This invention provides a stable oral gel composition for levocarnitine, which, after 6 months of testing at 40°C and 75% relative humidity, showed no dehydration or shrinkage, and exhibited stable drug dissolution and trimethylamine impurities. The high drug loading capacity reduces the amount of composition required for a single dose. 2. High medication adherence. The composition of this invention is easy to swallow, convenient to carry and take. Compared with tablets and chewable tablets, it can be taken directly after opening, without the need for water, especially when patients with chronic renal failure cannot drink water during treatment. Compared with existing dosage forms such as oral solutions, oral gels are more convenient to carry; simply tear open the packaging and squeeze it into the mouth. 3. This invention provides a method for preparing an oral gel composition containing levocarnitine that is safer than existing technologies. It does not include sterilization steps that significantly increase the trimethylamine content, and the toxic impurity trimethylamine is significantly lower than the control threshold (0.06%), which is more conducive to the safety of children's medication. Detailed Implementation

[0014] The present invention will be further described below with reference to embodiments. It should be noted that the purpose of the following description is to explain the present invention, but it does not constitute a limitation on the present invention. Example 1

[0015] Prescription composition weight Lorcarnitine 25 Carrageenan 0.9 Xanthan Gum 0.1 Complete neutralization of sodium polyacrylate (SX) 0.005 Sodium citrate 1 Maltitol 10 glycerin 5 malic acid 0.5 Sucralose 0.05 Methylparaben 0.05 strawberry flavoring 0.02 Purified water margin total 100 .

[0016] Preparation method: Heat an appropriate amount of purified water to 80-85℃, add the gel matrix and sodium polyacrylate in sequence, stir to disperse and dissolve, cool to 30-45℃ and add L-carnitine to dissolve, add alkali metal salt and other ingredients, stir evenly; dispense into strip bags filled with composite film material, about 4g / bag, seal and allow to cool naturally to obtain oral gel. Example 2

[0017] Prescription composition weight Lorcarnitine 50 Carrageenan 0.5 Complete neutralization of sodium polyacrylate (MX) 0.01 Potassium chloride 0.1 sucrose 4.5 glycerin 5 malic acid 0.4 Sucralose 0.1 Ethylparaben 0.1 Banana flavoring 0.05 Purified water margin total 100 .

[0018] Preparation method: Heat an appropriate amount of purified water to 80-85℃, add the gel matrix and sodium polyacrylate in sequence, stir to disperse and dissolve, cool to 30-45℃ and add L-carnitine to dissolve, add alkali metal salt and other ingredients, stir evenly; dispense into strip bags filled with composite film material, about 2g / bag, seal and allow to cool naturally to obtain oral gel. Example 3

[0019] Prescription composition weight Lorcarnitine 33.3 pectin 0.9 Xanthan Gum 0.1 Partially neutralize sodium polyacrylate (AH-106X) 0.25 Sodium citrate 2 Maltitol 10 glycerin 10 malic acid 0.35 Sucralose 0.05 Propylparaben 0.01 Pineapple flavoring 1.2 Purified water margin total 100 .

[0020] Preparation method: Heat an appropriate amount of purified water to 80-85℃, add gel matrix and partially neutralized sodium polyacrylate in sequence and stir to disperse and dissolve. After cooling to 30-45℃, add L-carnitine to dissolve, add alkali metal salt and other ingredients, stir evenly and dispense into three-side-sealed stick-shaped plastic bags, about 3g / bag, seal and allow to cool naturally to obtain oral gel. Example 4

[0021] Prescription composition weight Lorcarnitine 40 pectin 5 Calcium lactate 3 Partially neutralize sodium polyacrylate (AHX) 0.1 Sorbitol 10 Xylitol 14.5 Propylene glycol 5 glacial acetic acid 0.05 Aspartame 0.5 Potassium sorbate 0.2 Orange flavoring 0.1 Purified water margin total 100 .

[0022] Preparation method: Heat an appropriate amount of purified water to 80-85℃, add gel matrix and partially neutralized sodium polyacrylate in sequence and stir to disperse and dissolve. After cooling to 30-45℃, add L-carnitine to dissolve, add alkali metal salt and other ingredients, and stir evenly. Dispense into strip bags filled with composite film material, about 2.5g / bag, seal and allow to cool naturally to obtain oral gel. Example 5

[0023] Prescription composition weight Lorcarnitine 40 pectin 0.3 Partially neutralize sodium polyacrylate (AH-105X) 0.1 Calcium citrate 1 Maltitol 10 Propylene glycol 5 Sorbic acid 0.9 Aspartame 0.1 Sodium benzoate 0.5 Vanillin 0.5 Purified water margin total 100 .

[0024] Preparation method: Heat an appropriate amount of purified water to 80-85℃, add the gel matrix and partially neutralized sodium polyacrylate in sequence and stir to disperse and dissolve. After cooling to 30-45℃, add L-carnitine to dissolve, add alkali metal salt and other ingredients, and stir evenly. Dispense into strip plastic bags filled with composite film material, about 2.5g / bag, seal and allow to cool naturally to obtain oral gel. Example 6

[0025] Prescription composition weight Lorcarnitine 25 Carrageenan 0.6 Xanthan Gum 0.4 Complete neutralization of sodium polyacrylate (SX) 0.2 Sodium chloride 1 sucrose 24.5 glycerin 0.5 malic acid 2.5 Aspartame 0.5 Methylparaben 0.25 Propylparaben 0.03 Apple flavoring 1 Purified water margin total 100 .

[0026] Preparation method: Heat an appropriate amount of purified water to 80-85℃, add the gel matrix and sodium polyacrylate in sequence, stir to disperse and dissolve, cool to 30-45℃ and add L-carnitine to dissolve, add alkali metal salt and other ingredients, stir evenly; dispense into strip plastic bags filled with composite film material, about 4g / bag, seal and allow to cool naturally to obtain oral gel. Example 7

[0027] Prescription composition weight Lorcarnitine 33 Xanthan Gum 0.8 Complete neutralization of sodium polyacrylate (MX) 0.1 Sodium citrate 3 Maltitol 5 glycerin 6 fumaric acid 5 Aspartame 4 Methylparaben 0.05 Grape flavoring 1.5 Purified water margin total 100 .

[0028] Preparation method: Heat an appropriate amount of purified water to 80-85℃, add the gel matrix and sodium polyacrylate in sequence, stir to disperse and dissolve, cool to 30-45℃ and add L-carnitine to dissolve, add alkali metal salt and other ingredients, stir evenly; dispense into strip bags filled with composite film material, about 1g / bag, seal and allow to cool naturally to obtain oral gel. Example 8

[0029] Prescription composition weight Lorcarnitine 25 Carrageenan 0.4 Xanthan Gum 0.2 Complete neutralization of sodium polyacrylate (SX) 0.005 Sodium citrate 1 Sorbitol 20 glycerin 3 Citric acid 0.5 Aspartame 0.5 Methylparaben 0.05 strawberry flavoring 0.01 Purified water margin total 100 .

[0030] Preparation method: Heat an appropriate amount of purified water to 80-85℃, add the gel matrix and sodium polyacrylate in sequence, stir to disperse and dissolve, cool to 30-45℃ and add L-carnitine to dissolve, add alkali metal salt and other ingredients, stir evenly; dispense into plastic containers, about 4g / box, seal and allow to cool naturally to obtain oral gel. Comparative Examples 1-3

[0031] Comparative Example 1 Comparative Example 2 Comparative Example 3 Prescription composition weight weight weight Lorcarnitine 25 25 25 Carrageenan 0.5 / 0.5 Xanthan Gum 0.5 / 0.5 Sodium polyacrylate / / / gelatin / 4 / Sodium citrate 3.5 1 1 Sorbitol 10 10 1.5 glycerin 3 3 3 Citric acid 0.5 0.5 0.04 Sucralose 0.5 0.5 0.5 Propylparaben 0.02 0.02 0.02 strawberry flavoring 0.01 0.01 0.01 Purified water margin margin margin total 100 100 100 .

[0032] Preparation method: Heat an appropriate amount of purified water to 80-85℃, add the gel matrix and stir to disperse and dissolve it, then add L-carnitine to dissolve it, add alkali metal salt and other ingredients, stir evenly, and heat to 100℃ for sterilization for 15 minutes; dispense into strip bags filled with composite film material, about 4g / bag, seal and allow to cool naturally to obtain oral gel.

[0033] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications and substitutions should be covered within the scope of the claims of the present invention. Experimental Example 1

[0034] For Examples 1-8, compared with Examples 1-3, the appearance, pH, gel strength, and presence of water exudation of the oral gel were evaluated, and the results are shown in Table 1.

[0035] Evaluation criteria: Appearance: Visually inspected; gel-like, transparent, and smooth. pH: Cut a piece of gel equivalent to 1g of L-carnitine, dilute it with water to 20ml, and measure the pH using a pH meter; Gel strength: determined using the following apparatus and parameters: TA-XT-PLUS rheometer; inner diameter of the container used to fill the gel composition: 20 mm; piston: cylindrical, 10 mm in diameter; insertion speed: 30 cm / min; insertion distance: 10 mm; temperature: room temperature (approximately 25 °C). The maximum stress (gf) on the piston was measured and obtained by dividing the measured maximum stress by the cross-sectional area of ​​the piston (cm²).

[0036] The results showed that all of the above embodiments could be formed, with sample 1 being the most ideal sample, while comparative embodiment 2 could not be formed.

[0037] The pH of the gel compositions in Examples 1-8 is between 4.5 and 7, with Examples 6 and 8 having a pH between 5 and 6, resulting in the best taste.

[0038] The gel compositions of Examples 1-8 have a gel strength of 50-250 gf / cm. 2 Suitable for use as a pharmaceutical. The gel strength of Examples 1, 4, 5, and 7 is 140-210 gf / cm³. 2 It is best suited for oral administration, is easy to swallow, and has a gel strength of 278 gf / cm² (comparative example 1). 2 It has a hard texture and is difficult to swallow.

[0039] Table 1. Evaluation results of appearance, pH, gel strength, dehydration shrinkage, and mouthfeel of samples from Examples 1-8 and Comparative Examples 1-3. Appearance pH <![CDATA[Gel strength (gf / cm 2 )]]> Dehydration and shrinkage Taste and swallowability Example 1 Even and smooth gel 4.50 186 none Sweet and sour, easy to swallow Example 2 Even and smooth gel 4.82 73 none Sweet and sour, easy to swallow Example 3 Even and smooth gel 4.98 92 none Sweet and sour, easy to swallow Example 4 Even and smooth gel 4.61 166 none Sweet and sour, easy to swallow Example 5 Even and smooth gel 7.00 173 none Sweet and sour, easy to swallow Example 6 Even and smooth gel 5.49 120 none Sweet and sour, easy to swallow Example 7 Even and smooth gel 6.14 203 none Sweet and sour, easy to swallow Example 8 Even and smooth gel 5.73 241 none Sweet and sour, easy to swallow Comparative Example 1 Even and smooth gel 4.99 278 none Hard, difficult to swallow Comparative Example 2 Unformed / / / / Comparative Example 3 Even and smooth gel 7.26 130 none Slightly astringent, easy to swallow . Experimental Example 2

[0040] For Examples 1-8, Comparative Example 3 (weighing gel equivalent to 1g of L-carnitine), and the reference formulation L-carnitine chewable tablets (1g), dissolution evaluation tests were performed. 900ml of pH 1.0 hydrochloric acid solution was used as the dissolution medium, and the rotation speed was 75 rpm. Samples were taken at 10, 15, 20, 30, and 45 minutes to prepare test solutions and reference solutions. The dissolution amount was calculated using the external standard method based on peak area, and the f2 factor was calculated. The similarity of the dissolution curves of each example and the reference formulation was compared.

[0041] The results are shown in Table 2. The dissolution curves of Examples 1-8 and the reference preparation (chewable tablets) all have an f2 factor greater than 50, which can be judged as similar. The sweetener content of Comparative Example 3 is less than 2.5%, and the f2 factor is less than 50. The dissolution curve is not similar to that of the reference preparation.

[0042] Table 2. Similarity evaluation results of dissolution curves between samples from Examples 1-8 and Comparative Example 3 and the reference formulation. Sampling points (min) 10 15 20 30 45 f2 Chewable tablets (reference preparation) Cumulative dissolution (%) 58 79 88 93 97 / Example 1 Cumulative dissolution (%) 65 82 89 94 95 72 Example 2 Cumulative dissolution (%) 60 80 86 89 92 74 Example 3 Cumulative dissolution (%) 58 81 85 92 98 85 Example 4 Cumulative dissolution (%) 67 76 80 86 88 56 Example 5 Cumulative dissolution (%) 64 69 83 84 95 57 Example 6 Cumulative dissolution (%) 53 71 79 90 91 59 Example 7 Cumulative dissolution (%) 56 77 83 90 95 75 Example 8 Cumulative dissolution (%) 58 74 80 92 93 66 Comparative Example 3 Cumulative dissolution (%) 45 66 72 81 88 45 . Experimental Example 3

[0043] The gel compositions of Examples 1, 5, 6 and Comparative Example 3 were placed at a temperature of 40°C and a relative humidity of 75% for 6 months. The changes in appearance, dehydration shrinkage, content, trimethylamine impurity (TMA), dissolution rate, and other indicators were evaluated at 1 month, 3 months, and 6 months compared with those at 0.

[0044] The results are shown in Table 3. The appearance, dehydration shrinkage, content, trimethylamine impurity (TMA), and dissolution of the gel compositions in Examples 1, 5, and 6 showed no significant changes compared to the 0 value. In contrast, Example 3, which did not contain sodium polyacrylate, exhibited dehydration shrinkage, TMA exceeding the control threshold of 0.06% and gradually increasing, and slower dissolution.

[0045] Table 3 shows the stability of samples from Examples 1, 5, 6, and Comparative Example 3 at 40℃ / 75% RH. , ☆A uniform and delicate gel, *with a control threshold of 0.06%. Test Example 4

[0046] Biological equivalence study in humans of L-carnitine chewable tablets (Carnitor®, Alfasigma SpA, chewable tablet, 1g) and the oral gel of Example 5 (1g L-carnitine / 2.5g gel). A single-center, randomized, open-label, single-dose, two-formulation, two-period, two-sequence crossover design human bioequivalence study was conducted in 12 healthy subjects under fasting conditions using either the oral gel of Example 5 (1g L-carnitine / 2.5g gel) or the L-carnitine chewable tablets (Carnitor®, Alfasigma SpA, chewable tablet, 1g).

[0047] All enrolled subjects were randomly assigned to Group I and Group II, with an equal number of subjects in each group. Each subject received either the test formulation (T) or the reference formulation (R) once per cycle. Serum concentrations of levocarnitine were measured, and the bioequivalence of the two formulations was confirmed based on pharmacokinetics.

[0048] The results showed that the oral gel (1g L-carnitine / 2.5g gel) of Example 5 was bioequivalent to the L-carnitine chewable tablets (Carnitor®, Alfasigma SpA, chewable tablets, 1g). Using 90% confidence interval analysis, the geometric mean ratios of the test and reference formulations for the primary pharmacokinetic parameters Cmax and AUC0-t, and their 90% confidence intervals, were 98.05% (86.62%–113.96%) and 96.16% (92.85%–107.66%), respectively. All parameters had 90% confidence intervals within the range of 80.00%–125.00%.

Claims

1. A stable levocarnitine oral gel composition, characterized in that, It contains levocarnitine, a gel matrix, an alkali metal salt, and sodium polyacrylate.

2. The L-carnitine oral gel composition according to claim 1, characterized in that, The content of levocarnitine is 25-50% of the total weight of the composition.

3. The L-carnitine oral gel composition according to claim 1, characterized in that, The gel matrix is ​​selected from at least one of carrageenan, pectin, and xanthan gum, and its content accounts for 0.4-5% of the total weight of the composition.

4. The L-carnitine oral gel composition according to claim 1, characterized in that, The alkali metal salt is selected from at least one of sodium chloride, potassium chloride, sodium citrate, calcium citrate, and calcium lactate, and its content accounts for 0.1-3% of the total weight of the composition.

5. The stable L-carnitine oral gel composition according to claim 1, characterized in that, The sodium polyacrylate is selected from fully neutralized sodium polyacrylate or partially neutralized sodium polyacrylate.

6. The L-carnitine oral gel composition according to claim 1, characterized in that, The sodium polyacrylate content accounts for 0.005-0.25% of the total weight of the composition.

7. The L-carnitine oral gel composition according to claim 1, characterized in that, It also contains pH adjusters, humectants, sweeteners, preservatives, flavorings, and the remainder water.

8. The non-sterile preparation method of the L-carnitine oral gel according to any one of claims 1-7, characterized in that, The process includes the following steps: heating an appropriate amount of purified water, adding the gel matrix and sodium polyacrylate in sequence and stirring to disperse and dissolve them, cooling down and adding L-carnitine to dissolve it, adding alkali metal salts and other ingredients, and stirring evenly; dispensing into predetermined plastic packaging containers, sealing and allowing them to cool naturally to obtain an oral gel.