Dissolution medium for detecting dissolution rate of coenzyme Q10 tablet and detection method for dissolution rate of coenzyme Q10 tablet

Abstract

The invention relates to the technical field of medicine analysis, in particular to a dissolution medium for detecting the dissolution rate of coenzyme Q10 tablets and a detection method for the dissolution rate of the coenzyme Q10 tablets, the dissolution medium for detecting the dissolution rate of the coenzyme Q10 tablets comprises a surfactant, the surfactant is triton, the concentration of the surfactant is 0.7 wt%-1.0 wt%, and the pH value of the dissolution medium is 5.8-6.8. By controlling the concentration of triton in the dissolution medium and the pH value of the dissolution medium, the dissolution medium has high dissolution rate on the coenzyme Q10 tablet, and particularly, the addition amount of triton is controlled to be 0.7-1.0 wt%, so that the quality evaluation accuracy of the coenzyme Q10 tablet is increased to the maximum extent, and the intrinsic quality of a self-made preparation and the intrinsic quality of a reference preparation can be effectively distinguished.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical analysis technology, and in particular to a dissolution medium for detecting the dissolution rate of coenzyme Q10 tablets and a method for detecting the dissolution rate of coenzyme Q10 tablets. Background Technology

[0002] Coenzyme Q10 (English name: ), chemical name and structural formula are shown below:

[0003] Coenzyme Q10 tablets were approved for marketing in Japan by the PMDA in April 1978. Available in 5mg and 10mg tablets, marketed under the brand name Neuquinon, they are used to treat mild to moderate symptoms of congestive heart failure during basic treatment. The standard for Coenzyme Q10 tablets is only listed in the Chinese Pharmacopoeia and the United States Pharmacopeia (USP). Referring to the dissolution test method in USP (USP-NF2024): the blue method, 75 rpm, 500 ml water, the result was a dissolution rate of 0.01% within 180 minutes, indicating almost no dissolution. This is because Coenzyme Q10 exists in both water-soluble and lipid-soluble forms, and the original drug used lipid-soluble Coenzyme Q10. The dissolution method in the USP is not applicable to the dissolution test of lipid-soluble Coenzyme Q10.

[0004] Therefore, it is of great significance to develop a reasonable method for determining the dissolution rate of fat-soluble coenzyme Q10 tablets. Summary of the Invention

[0005] The present invention aims to at least partially solve one of the technical problems in the prior art. Therefore, one object of the present invention is to provide a dissolution medium for detecting the dissolution rate of coenzyme Q10 tablets and a method for detecting the dissolution rate of coenzyme Q10 tablets.

[0006] In a first aspect, the present invention provides a dissolution medium for detecting the dissolution rate of coenzyme Q10 tablets. The dissolution medium comprises: a surfactant, wherein the surfactant is Triton, the concentration of the surfactant is 0.7 wt% to 1.0 wt%, and the pH value of the dissolution medium is 5.8 to 6.8.

[0007] For example, the concentration of the surfactant is 0.7wt%, 0.75wt%, 0.8wt%, 0.85wt%, 0.9wt%, 0.95wt%, 1.0wt%, etc., or any range between any two of the above values; the pH value of the dissolution medium is 5.8, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, etc., or any range between any two of the above values.

[0008] According to the dissolution medium for detecting the dissolution rate of coenzyme Q10 tablets described above, by adding 0.7wt% to 1.0wt% of Triton to the dissolution medium and controlling the pH value of the dissolution medium to 5.8 to 6.8, the dissolution rate of coenzyme Q10 tablets in the dissolution medium can be significantly improved. At the same time, the amount of Triton added in this invention is between 0.7wt% and 1.0wt% (in the process of selecting the dissolution medium, in order to control the influence of surfactant on the detection results, in principle, the less surfactant added, the better), which maximizes the accuracy of quality evaluation of coenzyme Q10 tablets and can effectively distinguish the intrinsic quality of self-made preparations and reference preparations.

[0009] Preferably, the concentration of the surfactant in the leaching medium is 0.8wt%~0.9wt%.

[0010] Preferably, the pH value of the leaching medium is 6.0 to 6.8.

[0011] Preferably, the concentration of the surfactant is 0.8wt%~0.9wt%, and the pH of the dissolution medium is 6.0~6.8, which can significantly improve the dissolution rate of coenzyme Q10 tablets in the dissolution medium.

[0012] According to the above-described dissolution medium for detecting the dissolution rate of coenzyme Q10 tablets, the buffer solution used to adjust the pH value of the dissolution medium includes one of acetate buffer and phosphate buffer.

[0013] As an example, acetate buffer includes sodium acetate and acetic acid.

[0014] As an example, phosphate buffer includes sodium dihydrogen phosphate and sodium hydroxide.

[0015] According to the dissolution medium for detecting the dissolution rate of coenzyme Q10 tablets described above in this invention, the coenzyme Q10 tablets comprise coenzyme Q10, lactose, microcrystalline cellulose, corn starch, hydroxypropyl cellulose, calcium carboxymethyl cellulose, silicon dioxide, and stearic acid.

[0016] Furthermore, the coenzyme Q10 tablets comprise 10 wt% coenzyme Q10, 9 wt% to 11 wt% lactose, 28 wt% to 30 wt% microcrystalline cellulose, 29 wt% to 31 wt% corn starch, 7 wt% to 9 wt% hydroxypropyl cellulose, 7 wt% to 9 wt% calcium carboxymethyl cellulose, 3 wt% to 5 wt% silicon dioxide, and 0.9 wt% to 1.1 wt% stearic acid.

[0017] In a second aspect, the present invention provides a method for detecting the dissolution rate of coenzyme Q10 tablets. The method includes: The above dissolution medium was mixed with coenzyme Q10 tablets and stirred. Samples were taken at different time points, and the dissolution rate of coenzyme Q10 tablets at different time points was detected by high performance liquid chromatography.

[0018] According to the above-described method for detecting the dissolution rate of coenzyme Q10 tablets, this method is simple to operate, can significantly improve the detection effect of coenzyme Q10 tablet dissolution rate, reduce the RSD of dissolution rate between samples, and effectively distinguish the intrinsic quality of self-made formulations and reference formulations.

[0019] According to the method for detecting the dissolution rate of coenzyme Q10 tablets of the present invention, the stirring method includes paddle stirring and basket stirring, with paddle stirring being preferred. Samples prepared using paddle stirring have less deviation and better reproducibility.

[0020] According to the method for detecting the dissolution rate of coenzyme Q10 tablets described above, the paddle stirring speed is 60 rpm to 100 rpm, preferably 70 rpm to 80 rpm. For example, speeds of 60 rpm, 65 rpm, 70 rpm, 75 rpm, 80 rpm, 85 rpm, 90 rpm, 95 rpm, 100 rpm, or any range between any two of these values. Samples prepared using a paddle stirring method with a speed of 60 rpm to 100 rpm exhibit less deviation and better reproducibility.

[0021] According to the method for detecting the dissolution rate of coenzyme Q10 tablets described above, the rotation speed of the basket method is 80 rpm to 100 rpm. For example, the rotation speed is 80 rpm, 85 rpm, 90 rpm, 95 rpm, 100 rpm, etc., or any range between any two of the above values.

[0022] According to the above-mentioned method for detecting the dissolution rate of coenzyme Q10 tablets, the sampling times are 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min, and 180 min, respectively.

[0023] According to the above-mentioned method for detecting the dissolution rate of coenzyme Q10 tablets, the chromatographic conditions of the high-performance liquid chromatography (HPLC) are as follows: chromatographic column: octadecylsilane-bonded silica gel, preferably Agilent SB C18, 4.6 mm × 150 mm, 5 µm; mobile phase: methanol: anhydrous ethanol = 50:50; wavelength: 275 nm; column temperature: 35℃~37℃; flow rate: 1.5 ml / min, injection volume 20 μL, isocratic elution.

[0024] The present invention has at least the following technical effects: (1) The dissolution medium of the present invention has a high dissolution rate for coenzyme Q10 tablets, achieving a dissolution rate of 85% after 2 hours and a dissolution rate of more than 95% after 3 hours; at the same time, the amount of Triton added in the present invention is between 0.7wt% and 1.0wt%, and the pH value of the dissolution medium is between 6.0 and 6.8, which maximizes the accuracy of quality evaluation of coenzyme Q10 tablets and can effectively distinguish the intrinsic quality of self-made preparations from reference preparations.

[0025] (2) The method for detecting the dissolution of coenzyme Q10 tablets of the present invention is simple to operate and can significantly improve the detection effect of the dissolution of coenzyme Q10 tablets and reduce the RSD of dissolution between samples. Detailed Implementation

[0026] Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of this invention. The invention will now be described with reference to specific embodiments. It should be noted that these embodiments are merely descriptive and do not limit the invention in any way.

[0027] Example 1

[0028] Example 1: The dissolution rate of coenzyme Q10 tablets in 0.7wt%, 0.8wt%, and 1.0wt% Triton dissolution media at pH 6.8 was tested. The specific process is as follows: (1) Preparation of dissolution medium

[0029] Preparation of pH 6.8 solution: Weigh 6g of sodium dihydrogen phosphate and 0.9g of sodium hydroxide, add 1000ml of degassed water to dissolve (ultrasounding can be used if necessary), stir evenly, and adjust the pH value to 6.8±0.05.

[0030] Preparation of 0.7wt% Triton pH 6.8 solution: Weigh 7g Triton, add to 1000ml pH 6.8 solution to dissolve, stir well, and the solution is ready.

[0031] Preparation of 0.8wt% Triton pH 6.8 solution: Weigh 8g of Triton, add 1000ml of pH 6.8 solution to dissolve, stir well, and the solution is ready.

[0032] Preparation of 1.0wt% Triton pH 6.8 solution: Weigh 10g Triton, add to 1000ml pH 6.8 solution to dissolve, stir well, and the solution is ready.

[0033] (2) Preparation of the test solution

[0034] Take one Coenzyme Q10 tablet and place it in a dissolution vessel. Add dissolution media of different Triton concentrations as described above and perform dissolution operation at 75 rpm (paddle method). Then, at 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min, and 180 min, respectively, take out about 10 ml of sample solution and filter it. Take the filtrate as the test solution.

[0035] (3) Preparation of reference solution

[0036] Take 11.11 mg of coenzyme Q10 reference standard and place it in a 20 ml volumetric flask. Add 20 ml of methanol-anhydrous ethanol (50:50) to dissolve it. Accurately measure 1 ml of the solution and place it in a 100 ml volumetric flask. Add dissolution medium and dilute to the mark. Shake well to obtain the final product.

[0037] (4) Instruments and chromatographic conditions

[0038] Shimadzu LC-20AT high performance liquid chromatograph, quaternary pump, DAD detector, autosampler.

[0039] An octadecylsilane-bonded silica gel column (4.6 mm × 150 mm, 5 µm) was used as the packing material. The mobile phase was methanol-anhydrous ethanol (50:50). The flow rate was 1.5 mL / min, the detection wavelength was 275 nm, and the column temperature was 35 °C.

[0040] (5) Detection methods

[0041] Take 20 μl of the reference solution and the test solution respectively, inject them into the liquid chromatograph, record the chromatograms, and calculate the dissolution rate of coenzyme Q10 by peak area according to the external standard method.

[0042] Comparative Example 1

[0043] Differences between Comparative Example 1 and Example 1: Comparative Example 1: The dissolution rate of Coenzyme Q10 tablets in 0.5wt% and 1.2wt% Triton dissolution media at pH 6.8 was tested.

[0044] (1) Preparation of dissolution medium

[0045] Preparation of pH 6.8 solution: Weigh 6g of sodium dihydrogen phosphate and 0.9g of sodium hydroxide, add 1000ml of degassed water to dissolve (ultrasounding can be used if necessary), stir evenly, and adjust the pH value to 6.8±0.05.

[0046] Preparation of 0.5wt% Triton pH 6.8 solution: Weigh 5g Triton, add to 1000ml pH 6.8 solution to dissolve, stir well, and the solution is ready.

[0047] Preparation of 1.2wt% Triton pH 6.8 solution: Weigh 12g Triton, add to 1000ml pH 6.8 solution to dissolve, stir well, and the solution is ready.

[0048] The dissolution test results of Coenzyme Q10 tablets of Example 1 and Comparative Example 1 in dissolution media of different concentrations of Triton are shown in Table 1.

[0049] Table 1

[0050] Note: In Tables 1 to 6, N=12 means that each test group consists of 12 parallel experiments. The dissolution data in Table 1 is the average dissolution data of the 12 parallel experiments.

[0051] As shown in Table 1, the coenzyme Q10 tablets of Example 1 exhibited dissolution rates above 85% after 2 hours and above 95% after 3 hours in 0.7 wt% Triathon dissolution media at pH 6.8, 0.8 wt% Triathon dissolution media at pH 6.8, and 1.0 wt% Triathon dissolution media at pH 6.8. In contrast, the coenzyme Q10 tablets of Comparative Example 1 showed very low dissolution rates in the dissolution media when the Triathon concentration was reduced; after increasing the Triathon concentration, the dissolution rate was below 85% after 2 hours and slightly below 95% after 3 hours.

[0052] Example 2

[0053] Example 2: The dissolution rate of coenzyme Q10 tablets in 0.8 wt% Triton dissolution media at pH 6.8 and pH 6.0 was tested, and the specific process is as follows: (1) Preparation of dissolution medium

[0054] Preparation of 0.8wt% Triton dissolution medium at pH 6.8: Weigh 6g of sodium dihydrogen phosphate and 0.9g of sodium hydroxide, add 1000ml of degassed water to dissolve (ultrasonication may be used if necessary), and stir evenly. Adjust the pH value to 6.8±0.05 to obtain a solution with pH 6.8; add 8g of Triton to 1000ml of the pH 6.8 solution to dissolve, and stir evenly to obtain the solution.

[0055] Preparation of 0.8wt% Triton dissolution medium at pH 6.0: Dissolve 109.2g of sodium acetate in 40ml of 1mol / L acetic acid solution, then dilute with degassed water to 1000ml (ultrasonication may be used if necessary), and stir until homogeneous; add 8g of Triton to 1000ml of pH 6.0 solution and stir until homogeneous to obtain the solution.

[0056] (2) Preparation of the test solution

[0057] Take one Coenzyme Q10 tablet and place it in a dissolution vessel. Add the above dissolution medium and perform dissolution at 75 rpm (paddle method). Then, at 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min, and 180 min, respectively, take out about 10 ml of sample solution and filter it. Take the filtrate as the test solution.

[0058] (3) Preparation of reference solution

[0059] Take 11.11 mg of coenzyme Q10 reference standard and place it in a 20 ml volumetric flask. Add 20 ml of methanol-anhydrous ethanol (50:50) to dissolve it. Accurately measure 1 ml of the solution and place it in a 100 ml volumetric flask. Add dissolution medium and dilute to the mark. Shake well to obtain the final product.

[0060] (4) Instruments and chromatographic conditions

[0061] Shimadzu LC-20AT high performance liquid chromatograph, quaternary pump, DAD detector, autosampler.

[0062] An octadecylsilane-bonded silica gel column (4.6 mm × 150 mm, 5 µm) was used as the packing material. The mobile phase was methanol-anhydrous ethanol (50:50). The flow rate was 1.5 mL / min, the detection wavelength was 275 nm, and the column temperature was 35 °C.

[0063] (5) Detection methods

[0064] Take 20 μl of the reference solution and the test solution respectively, inject them into the liquid chromatograph, record the chromatograms, and calculate the dissolution rate of coenzyme Q10 by peak area according to the external standard method.

[0065] Comparative Example 2

[0066] Comparative Example 2: The dissolution rate of Coenzyme Q10 tablets in 0.8 wt% Triton dissolution media at pH 7.8 and pH 4.5 was determined.

[0067] The difference between Comparative Example 2 and Example 2 is as follows: (1) Preparation of dissolution medium

[0068] Preparation of 0.8wt% Triton dissolution medium at pH 7.8: Take 5.59g of dipotassium hydrogen phosphate and 0.41g of potassium dihydrogen phosphate, add degassed water to dissolve to 1000ml (ultrasonication may be used if necessary), and stir evenly; add 8g of Triton to 1000ml of pH 7.8 solution and dissolve, stir evenly to obtain the solution.

[0069] Preparation of 0.8wt% Triton dissolution medium at pH 4.5: Weigh 1.80g of anhydrous sodium acetate and measure 1.6ml of acetic acid, add 1000ml of degassed water (ultrasonication may be used if necessary), stir well, and adjust the pH to 4.5±0.05; add 8g of Triton to 1000ml of pH 4.5 solution to dissolve, stir well, and the solution is ready.

[0070] The dissolution results of the coenzyme Q10 tablets of Example 2 and Comparative Example 2 in different dissolution media are shown in Table 2.

[0071] Table 2

[0072] As shown in Table 2, the coenzyme Q10 tablets of Example 2 showed a dissolution rate of over 85% after 2 hours in both 0.8 wt% Triathon dissolution media at pH 6.0 and pH 6.8, and over 95% after 3 hours. In contrast, in Comparative Example 2, with both pH values ​​decreasing and increasing, the dissolution rates in both 0.8 wt% Triathon dissolution media at pH 4.5 and pH 7.8 were less than 85% after 2 hours, and did not reach over 95% after 3 hours.

[0073] Comparative Example 3

[0074] Comparative Example 3 verifies the dissolution rate of Coenzyme Q10 tablets in water, solution at pH 1.0, solution at pH 4.5, and solution at pH 6.8.

[0075] (1) Preparation of dissolution medium

[0076] Preparation of pH 1.0 solution: Take 9 ml of hydrochloric acid, add degassed water to dilute to 1000 ml (ultrasound can be used if necessary), stir well, and the solution is ready; Preparation of pH 4.5 solution: Weigh 1.80g of anhydrous sodium acetate and measure 1.6ml of acetic acid, add 1000ml of degassed water (ultrasonication may be used if necessary), stir well, and adjust the pH value to 4.5±0.05. Preparation of pH 6.8 solution: Weigh 6g of sodium dihydrogen phosphate and 0.9g of sodium hydroxide, add 1000ml of degassed water to dissolve (ultrasounding can be used if necessary), stir evenly, and adjust the pH value to 6.8±0.05.

[0077] (2) Preparation of the test solution

[0078] Take one Coenzyme Q10 tablet and place it in a dissolution vessel. Add the above dissolution medium and perform dissolution at 75 rpm (paddle method). Then, at 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min, and 180 min, respectively, take out about 10 ml of sample solution and filter it. Take the filtrate as the test solution.

[0079] (3) Preparation of reference solution: Take 11.11 mg of coenzyme Q10 reference standard and place it in a 20 ml volumetric flask. Add 20 ml of methanol-anhydrous ethanol (50:50) to dissolve it. Accurately measure 1 ml of the solution and place it in a 100 ml volumetric flask. Add dissolution medium and dilute to the mark. Shake well to obtain the final product.

[0080] (4) Instruments and chromatographic conditions

[0081] Shimadzu LC-20AT high performance liquid chromatograph, quaternary pump, DAD detector, autosampler.

[0082] An octadecylsilane-bonded silica gel column (4.6 mm × 150 mm, 5 µm) was used as the packing material. The mobile phase was methanol-anhydrous ethanol (50:50). The flow rate was 1.5 mL / min, the detection wavelength was 275 nm, and the column temperature was 35 °C.

[0083] (5) Detection methods

[0084] Take 20 μl of the reference solution and the test solution respectively, inject them into the liquid chromatograph, record the chromatograms, and calculate the dissolution rate of coenzyme Q10 tablets by peak area according to the external standard method.

[0085] The results of the dissolution rate detection of coenzyme Q10 tablets in different dissolution media of Comparative Example 3 are shown in Table 3.

[0086] Table 3

[0087] As shown in Table 3, Coenzyme Q10 tablets release almost no enzymes in vitro at pH 1.0, pH 4.5 and in water, and release a very small amount in a medium at pH 6.8.

[0088] Comparative Example 4

[0089] Comparative Example 4 verifies the dissolution rate of Coenzyme Q10 tablets in a dissolution medium containing other surfactants.

[0090] The difference between Comparative Example 4 and Comparative Example 3 is as follows: (1) Preparation of dissolution medium

[0091] Preparation of a pH 6.8 dissolution medium for 0.8% SDS (sodium dodecylbenzenesulfonate): Weigh 6g of sodium dihydrogen phosphate and 0.9g of sodium hydroxide, add 1000ml of degassed water to dissolve (ultrasonication may be used if necessary), and stir until homogeneous. Adjust the pH value to 6.8±0.05 to obtain a pH 6.8 solution; weigh 8g of SDS, add 1000ml of the pH 6.8 solution to dissolve, and stir until homogeneous to obtain the solution.

[0092] Preparation of a pH 6.8 dissolution medium for 0.8% Tween 80: Weigh 6g of sodium dihydrogen phosphate and 0.9g of sodium hydroxide, add 1000ml of degassed water to dissolve (ultrasonication may be used if necessary), and stir until homogeneous. Adjust the pH value to 6.8±0.05 to obtain a pH 6.8 solution. Weigh 8g of Tween 80, add 1000ml of the pH 6.8 solution to dissolve, and stir until homogeneous to obtain the solution.

[0093] The results of the dissolution rate detection of coenzyme Q10 tablets in different dissolution media of Comparative Example 4 are shown in Table 4.

[0094] Table 4

[0095] As shown in Table 4, the amount of coenzyme Q10 dissolved in 0.8% SDS and Tween 80 media was relatively small, indicating that the surfactants SDS and Tween 80 could not increase the dissolution of coenzyme Q10 tablets.

[0096] Example 3

[0097] Example 3 verifies the effect of different stirring methods on the dissolution rate of coenzyme Q10 tablets.

[0098] (1) Preparation of dissolution medium

[0099] Preparation of pH 6.8 dissolution medium for 0.8% Triton: Weigh 6g of sodium dihydrogen phosphate and 0.9g of sodium hydroxide, add 1000ml of degassed water to dissolve (ultrasonication may be used if necessary), and stir evenly. Adjust the pH value to 6.8±0.05 to obtain a pH 6.8 solution; Weigh 8g of Triton, add 1000ml of pH 6.8 solution to dissolve, and stir evenly to obtain the final solution.

[0100] (2) Preparation of the test solution

[0101] Take one Coenzyme Q10 tablet and place it in a dissolution vessel. Add the above dissolution medium and perform dissolution using a paddle mixer at 50 rpm. Then, at 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min, and 180 min, respectively, take out about 10 ml of sample solution and filter it. Use the filtrate as the test solution.

[0102] Take one Coenzyme Q10 tablet and place it in a dissolution vessel. Add the dissolution medium and perform the dissolution operation at a paddle speed of 75 rpm. Then, at 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min, and 180 min, respectively, take out about 10 ml of sample solution and filter it. Take the filtrate as the test solution.

[0103] Take one Coenzyme Q10 tablet and place it in a dissolution vessel. Add the dissolution medium and perform the dissolution operation at a speed of 100 rpm using the blue method. Then, at 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min, and 180 min, respectively, take out about 10 ml of sample solution and filter it. Take the filtrate as the test solution.

[0104] (3) Preparation of reference solution: Take 11.11 mg of coenzyme Q10 reference standard and place it in a 20 ml volumetric flask. Add 20 ml of methanol-anhydrous ethanol (50:50) to dissolve it. Accurately measure 1 ml and place it in a 100 ml volumetric flask. Add 0.8% Triton pH 6.8 solution to dilute to the mark and shake well.

[0105] (4) Instruments and chromatographic conditions

[0106] Shimadzu LC-20AT high performance liquid chromatograph, quaternary pump, DAD detector, autosampler.

[0107] An octadecylsilane-bonded silica gel column (4.6 mm × 150 mm, 5 µm) was used as the packing material. The mobile phase was methanol-anhydrous ethanol (50:50). The flow rate was 1.5 mL / min, the detection wavelength was 275 nm, and the column temperature was 35 °C.

[0108] (5) Detection methods

[0109] Take 20 μl of the reference solution and the test solution respectively, inject them into the liquid chromatograph, record the chromatograms, and calculate the dissolution rate of coenzyme Q10 by peak area according to the external standard method.

[0110] The results of the dissolution test of coenzyme Q10 tablets under different stirring methods are shown in Table 5.

[0111] Table 5

[0112] Table 5 shows that the sample prepared using the paddle method (75 rpm) has the smallest deviation and the best reproducibility. During the dissolution process of Coenzyme Q10 tablets using the paddle method (50 rpm) and the blue method (100 rpm), the tablet disintegration time differed significantly, exhibiting a stacking effect, thus causing a certain degree of dissolution deviation.

[0113] Example 4

[0114] Example 4 verifies whether the quality of the self-made formulation and the reference formulation are consistent.

[0115] (1) Preparation of dissolution medium

[0116] Preparation of the pH 6.8 dissolution medium for 0.8% Triton: Weigh 6g of sodium dihydrogen phosphate and 0.9g of sodium hydroxide, add 1000ml of degassed water to dissolve (ultrasonication may be used if necessary), and stir evenly. Adjust the pH value to 6.8±0.05 to obtain a pH 6.8 solution; Weigh 8g of Triton, add it to 1000ml of the pH 6.8 solution to dissolve, and stir evenly to obtain the solution.

[0117] (3) Preparation of the test solution

[0118] Take one Coenzyme Q10 tablet (the self-made formulation is Coenzyme Q10 tablet prepared by Beijing Nuokanda Pharmaceutical Technology Co., Ltd., with a specification of 10mg) and place it in a dissolution vessel. Add the above dissolution medium and perform dissolution operation by paddle rotation at 75 rpm. Then, take out about 10 ml of sample solution at 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min, and 180 min respectively, filter it, and take the filtrate as the test solution of the self-made formulation.

[0119] Take one Coenzyme Q10 tablet (the reference preparation is Coenzyme Q10 tablets with the trade name Neuquinon produced by Aezai Co., Ltd., with a specification of 10mg) and place it in a dissolution vessel. Add the above dissolution medium and perform dissolution operation by paddle stirring at a speed of 75 rpm. Then, take out about 10 ml of sample solution at 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min and 180 min respectively, filter it, and take the filtrate as the reference preparation test solution.

[0120] (3) Preparation of reference solution: Take 11.11 mg of coenzyme Q10 reference standard, place it in a 20 ml volumetric flask, and dissolve it in 20 ml of methanol-anhydrous ethanol (50:50). Accurately measure 1 ml of the solution and place it in a 100 ml volumetric flask. Dilute it to the mark with 0.8% Triton pH 6.8 solution and shake well.

[0121] (4) Instruments and chromatographic conditions

[0122] Shimadzu LC-20AT high performance liquid chromatograph, quaternary pump, DAD detector, autosampler.

[0123] An octadecylsilane-bonded silica gel column (4.6 mm × 150 mm, 5 µm) was used as the packing material. The mobile phase was methanol-anhydrous ethanol (50:50). The flow rate was 1.5 mL / min, the detection wavelength was 275 nm, and the column temperature was 35 °C.

[0124] (5) Detection methods

[0125] Take 20 μl of the reference solution and the test solution respectively, inject them into the liquid chromatograph, record the chromatograms, and calculate the dissolution rate of coenzyme Q10 by peak area according to the external standard method.

[0126] The dissolution test results of the self-made formulation and the reference formulation are shown in Table 6.

[0127] Table 6

[0128] As shown in Table 6, the quality of the self-made formulation is consistent with that of the reference formulation.

[0129] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A dissolution medium for detecting the dissolution rate of coenzyme Q10 tablets, characterized in that, include: The surfactant is Triton, the concentration of which is 0.7wt% to 1.0wt%, and the pH of the dissolution medium is 5.8 to 6.

8.

2. The dissolution medium according to claim 1, characterized in that, The concentration of the surfactant is 0.8wt%~0.9wt%.

3. The dissolution medium according to claim 1, characterized in that, The pH value of the leaching medium is 6.0~6.

8.

4. The dissolution medium according to any one of claims 1-3, characterized in that, The buffer solution used to adjust the pH of the dissolution medium includes one of acetate buffer and phosphate buffer.

5. The dissolution medium according to any one of claims 1-3, characterized in that, The coenzyme Q10 tablets include coenzyme Q10, lactose, microcrystalline cellulose, corn starch, hydroxypropyl cellulose, calcium carboxymethyl cellulose, silicon dioxide, and stearic acid.

6. A method for detecting the dissolution rate of coenzyme Q10 tablets, characterized in that, include: The dissolution medium described in any one of claims 1-5 was mixed and stirred with coenzyme Q10 tablets, and samples were taken at different time points. The dissolution rate of coenzyme Q10 tablets at different time points was detected by high performance liquid chromatography.

7. The method according to claim 6, characterized in that, The stirring methods include paddle stirring and basket stirring, with paddle stirring being preferred.

8. The method according to claim 7, characterized in that, The rotational speed of the paddle is 60 rpm to 100 rpm.

9. The method according to any one of claims 6-8, characterized in that, The sampling times were 5 min, 10 min, 15 min, 20 min, 30 min, 60 min, 90 min, 120 min, 150 min, and 180 min, respectively.

10. The method according to any one of claims 6-8, characterized in that, The chromatographic conditions for the high-performance liquid chromatography method are as follows: Column: Octadecylsilane-bonded silica gel; Mobile phase: Methanol: Anhydrous ethanol = 50:50; Wavelength: 275nm; Flow rate: 1.5 ml / min.

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