Method for determining dissolution curve of hydrobromic acid vortioxetine tablet
By adding CTAB surfactant to the aqueous medium of vothexetine hydrobromide tablets, the problems of solution inhomogeneity and point jumping are solved, the smoothness and stability of the dissolution curve are achieved, and the detection accuracy and reliability are improved. and reduce costs and environmental impacts.
Patent Information
- Application Number
- CN202411211605.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-30
- Publication Date
- 2024-12-13
AI Technical Summary
There is solution inhomogeneity in the dissolution curve of existing vothexetine hydrobromide tablets, resulting in the dissolution amount being lower than the previous time point, the detection results are inaccurate, and traditional surfactants such as SDS and Tween 80 are in the dissolution curve. There is a jump in the field, affecting the accuracy of detection.
Add cetyl trimethylammonium bromide (CTAB) as the surfactant to the dissolution medium. By optimizing dissolution conditions such as concentration and sampling methods, the smoothness and stability of the dissolution curve are ensured, and high-performance liquid chromatography is used to perform Test.
It significantly improves the solubility of vothexetine hydrobromic acid tablets, eliminates the jump of the dissolution curve, improves the accuracy and reliability of the detection results, reduces costs, and reduces the impact on the environment.
Smart Images
Figure CN119125345A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of drug analysis, in particular to a method for detecting a dissolution curve of voroxetine hydrobromide tablets. Background Art
[0002] Vortioxetine was jointly developed by Lundbeck and Takeda. Vortioxetine hydrobromide tablets were first approved by the US FDA in September 2013 for the treatment of major depressive disorder (MDD) in adults, and were approved in Europe on December 18, 2013. In 2017, it was included in the "14th batch of priority review and approval drugs" by the National Medical Products Administration and is a drug that "has obvious therapeutic advantages compared to existing treatments". This drug is the first new molecular entity antidepressant drug approved by the NMPA since 2010;
[0003] In the prior art, the aqueous medium dissolution curve of vortioxetine hydrobromide tablets usually only uses degassed purified water as the dissolution medium, and no surfactant is added to the medium. However, in actual testing, the sample in the degassed water medium is prone to have a phenomenon in which the dissolution amount at a later time point is lower than the dissolution amount at a previous time point. Investigations have found that when the same dissolution cup is sampled multiple times at the same time, the RSD of the test results is greater than 2%, which proves that the solution is not uniform, resulting in inaccurate test results and a non-smooth dissolution curve. Summary of the invention
[0004] The present invention provides the following scheme: a method for determining the dissolution curve of vortioxetine hydrobromide tablets, comprising:
[0005] Take 1000 ml of degassed purified water, add 0.1 g of hexadecyltrimethylammonium bromide (CTAB) thereto, stir to fully dissolve, mix evenly, and obtain a water + 0.01% CTAB solution;
[0006] Take vortioxetine hydrobromide tablets, use water + 0.01% CTAB as the dissolution medium, the medium volume is 900 ml, the medium temperature is 37.0 ° C, use the paddle method, the speed is 50 revolutions per minute, and sample at 5min, 10min, 15min, 20min, 30min, 45min, and 60min in sequence. The sampling volume is 5ml each time. The sample is filtered through a 10μm primary filter membrane, and the filtrate is taken as the test solution;
[0007] Take about 13 mg of vortioxetine hydrobromide reference substance, accurately weigh it, put it in a 100 ml volumetric flask, add the mobile phase to dissolve and dilute to the scale, shake well, accurately measure 2 ml of the reference substance stock solution, put it in a 20 ml volumetric flask, add the dissolution medium to dilute to the scale, shake well, and the reference substance solution is obtained;
[0008] High performance liquid chromatography was used, with a chromatographic column filled with phenylsilane bonded silica gel, a mobile phase of pH 4.5 ammonium acetate buffer-water-methanol (10:30:60), a detection wavelength of 226 nm, a column temperature of 40°C, a flow rate of 1.0 ml / min, an injection volume of 50 μl, a running time of 7 min, and the cumulative dissolution amount at each time point was calculated. The similarity factor f2 with the dissolution curve of the reference preparation was also calculated, and f2 was greater than or equal to 50.
[0009] Furthermore, pure degassed water was used as the dissolution medium to test the dissolution of the reference preparation and the homemade preparation.
[0010] Furthermore, the dissolution medium was replaced with water + 0.3% sodium dodecyl sulfate (SDS) to detect the dissolution of the homemade preparation.
[0011] Furthermore, the dissolution medium was replaced with water+0.1% Tween 80 and water+0.3% Tween 80, and the dissolution of the homemade preparation was tested.
[0012] Furthermore, the dissolution medium was replaced with water + 0.3% cetyltrimethylammonium bromide (CTAB) to detect the dissolution of the homemade preparation.
[0013] Furthermore, water + 0.1% CTAB was used as the dissolution medium to detect the dissolution of the reference preparation and the homemade preparation.
[0014] Furthermore, water + 0.01% CTAB was used as the dissolution medium to detect the dissolution of the reference preparation and the homemade preparation, and their f2 was calculated.
[0015] According to the specific embodiments provided by the present invention, the present invention discloses the following technical effects:
[0016] 1. The present invention significantly improves the solubility of vortioxetine hydrobromide tablets in an aqueous medium by adding a CTAB surfactant to the dissolution medium, solves the problem of uneven solution in the dissolution cup, and thus eliminates the jump point phenomenon of the dissolution curve. When CTAB is used as the dissolution medium, the cumulative dissolution amount at each time point is stable, the dissolution curve is smooth, and the detection result is accurate and reliable, which significantly improves the repeatability and predictability of the dissolution test, and provides a more reliable detection method for drug quality control.
[0017] 2. Traditionally, SDS (sodium dodecyl sulfate) and Tween 80 (polysorbate 80) are often used as surfactants in dissolution media. However, when SDS and Tween 80 are used in the present invention, the dissolution curve still has a jump point phenomenon and an abnormal peak shape. The present invention selects CTAB (hexadecyltrimethylammonium bromide) as the surfactant of the dissolution medium, which not only eliminates the jump point phenomenon but also improves the smoothness of the dissolution curve. Specific experimental data show that CTAB exhibits good dissolution effects at different concentrations (such as 0.01%, 0.1% and 0.3%), which is superior to SDS and Tween 80.
[0018] 3. The present invention uses CTAB as a surfactant in the dissolution medium, which not only improves the stability of the dissolution curve and the detection accuracy, but also has the advantage of a smaller dosage. CTAB can significantly improve the smoothness and stability of the dissolution curve when the concentration is 0.01%. The lower concentration not only reduces the cost, but also reduces the impact on the environment, further enhancing the practicality and economy of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.
[0020] Figure 1 This is the peak pattern diagram of the homemade preparation in water + 0.3% SDS medium (injection volume 50 μl);
[0021] Figure 2 This is the peak pattern diagram of the homemade preparation in water + 0.3% SDS medium (injection volume 20 μl);
[0022] Figure 3 This is the peak profile of the homemade preparation in water + 0.1% Tween 80 medium;
[0023] Figure 4 It is the peak profile of the homemade preparation in water + 0.3% Tween 80 medium;
[0024] Figure 5 This is the peak pattern of the homemade preparation in water + 0.3% CTAB medium;
[0025] Figure 6 It is the fitting diagram of the dissolution curves of the homemade preparation and the reference preparation in water + 0.01% CTAB medium. DETAILED DESCRIPTION
[0026] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0027] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.
[0028] Example
[0029] like Figure 1-Figure 6 As shown, the method for preparing the dissolution curve of vortioxetine hydrobromide tablets in this embodiment comprises:
[0030] Preparation of dissolution medium:
[0031] First, take 1000 ml of degassed purified water, add 0.1 g of hexadecyltrimethylammonium bromide (CTAB) thereto, stir to fully dissolve, mix evenly, and obtain a water + 0.01% CTAB solution as a dissolution medium;
[0032] Preparation of test solution:
[0033] Take vortioxetine hydrobromide tablets, and follow the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), use water + 0.01% CTAB as the dissolution medium, take samples at 5min, 10min, 15min, 20min, 30min, 45min, and 60min, filter the samples through a 10μm primary filter membrane, and take the filtrate as the test solution. By optimizing the dissolution conditions, ensure the accuracy and repeatability of the dissolution curve;
[0034] Preparation of reference solution:
[0035] Take about 13 mg of vortioxetine hydrobromide reference substance, accurately weigh it, put it in a 100 ml volumetric flask, add the mobile phase to dissolve and dilute to the scale, shake well, accurately measure 2 ml of the reference substance stock solution, put it in a 20 ml volumetric flask, add the dissolution medium to dilute to the scale, shake well, and obtain the reference substance solution. The preparation of the reference substance solution ensures the stability and accuracy of the reference substance during the detection process;
[0036] Dissolution conditions:
[0037] Water + 0.01% CTAB was used as the dissolution medium, the paddle method was used, the rotation speed was 50 revolutions per minute, the medium temperature was 37.0°C, the medium volume was 900ml, and the sampling volume was 5ml each time. This condition optimized the dissolution behavior of vortioxetine hydrobromide tablets and ensured the smoothness of the dissolution curve and the accuracy of the test results.
[0038] Testing conditions:
[0039] The detection was carried out by high performance liquid chromatography, and the chromatographic column was filled with phenylsilane bonded silica gel (Welch Phenyl-Hexyl 4.6×50mm, 3μm or equivalent chromatographic column), mobile phase is pH4.5 ammonium acetate buffer-water-methanol (10:30:60), detection wavelength is 226nm, column temperature is 40℃, flow rate is 1.0ml / min, injection volume is 50μl, running time is 7min, the cumulative dissolution amount at each time point is calculated by external standard method, and the similarity factor f2 compared with the reference preparation dissolution curve is calculated to ensure that f2 is greater than or equal to 50, so as to verify the consistency with the reference preparation quality;
[0040] The present application significantly improves the smoothness of the dissolution curve of vortioxetine hydrobromide tablets by adding 0.01% CTAB to the dissolution medium, solves the problem of fluctuation of the dissolution curve data, and ensures the accuracy and consistency of the test results; by using CTAB as a surfactant, the solubility of vortioxetine hydrobromide tablets in the aqueous medium can be effectively improved, and the instability of the dissolution amount caused by the solubility difference can be avoided, thereby ensuring the stability of the cumulative dissolution amount at each time point; by using water + 0.01% CTAB as the dissolution medium, combined with the optimized paddle method conditions (rotation speed 50rpm, medium temperature 37.0℃, medium volume 900ml), the stability and repeatability of the dissolution behavior are ensured, and the jump point phenomenon in the traditional dissolution curve detection method is avoided; by the detection of high performance liquid chromatography, the high precision and high repeatability of the detection process are ensured, and the chromatographic conditions (mobile phase, detection wavelength, column temperature, flow rate, injection volume and running time) are optimized to ensure the accurate calculation of the cumulative dissolution amount at each time point;
[0041] Calculation of similarity factor f2:
[0042]
[0043] Where n is the number of sampling time points, Rt is the dissolution value of the reference preparation at time t, and Tt is the dissolution value of the homemade preparation at time t.
[0044] By calculating the similarity factor f2 (f2 is required to be greater than or equal to 50), it is verified that under the same dissolution conditions, the dissolution behavior of the vortioxetine hydrobromide tablets and the reference preparation of the present application method is similar, thereby further ensuring the scientificity and reliability of the detection method.
[0045] Embodiment 1
[0046] Degassed purified water was used as the dissolution medium to test the dissolution of the homemade tablets;
[0047] According to the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), degassed purified water was used as the dissolution medium, the medium volume was 900 ml, the rotation speed was 50 revolutions per minute, and samples were taken at 0 min, 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 90 min, and 120 min, respectively. The sampling volume was 5 ml each time, and the sample was filtered through a 10 μm primary filter membrane, and the filtrate was taken as the test solution;
[0048]
[0049]
[0050] Conclusion: There are multiple jump points in the 6 homemade preparation samples in water medium (the dissolution amount at the latter time point is smaller than that at the previous time point). The test results show that the dissolution curve fluctuates and the dissolution curve is not smooth, resulting in inaccurate test results.
[0051] The present application can see from the experimental data of Example 1 that when degassed purified water is used as the dissolution medium, the dissolution curve of the homemade vortioxetine hydrobromide tablets has an obvious jump point phenomenon, that is, the dissolution amount at the subsequent time point is lower than that at the previous time point, resulting in an uneven dissolution curve, large data fluctuations, and a high RSD (relative standard deviation) value. This jump point phenomenon will affect the accurate measurement of the dissolution rate, making it impossible to obtain a stable dissolution curve.
[0052] Embodiment 2
[0053] The homemade tablets were replaced with the reference preparation, and degassed purified water was used as the dissolution medium to test the dissolution;
[0054] According to the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), degassed purified water was used as the dissolution medium, the medium volume was 900 ml, the rotation speed was 50 revolutions per minute, and samples were taken at 0 min, 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 90 min, and 120 min, respectively. The sampling volume was 5 ml each time, and the sample was filtered through a 10 μm primary filter membrane, and the filtrate was taken as the test solution;
[0055]
[0056]
[0057] Conclusion: Although the homemade tablets were replaced with the reference preparation, the test results still showed that there was a jump point phenomenon in the dissolution curve, that is, the dissolution amount at the latter time point was lower than that at the previous time point, resulting in an uneven dissolution curve, large data fluctuations, and a high RSD (relative standard deviation) value;
[0058] Embodiment 3
[0059] A single tablet of homemade preparation and a reference preparation were taken for dissolution determination, and three samples were taken from the dissolution cup at each time point. It was found that in the degassed purified water medium, the parallel three dissolution test results of one homemade preparation and one reference preparation at each time point showed that the RSD at multiple time points was greater than 2.0%, proving that the reference preparation and homemade preparation samples were not uniform in the water medium. After evaluation, the influence of water quality was excluded, and it was decided to screen surfactants to solve the jump point problem caused by the uneven dissolution solution.
[0060]
[0061]
[0062]
[0063] Embodiment 4
[0064] The dissolution medium was replaced with degassed purified water + 0.3% sodium dodecyl sulfate (SDS) to test the dissolution of the homemade preparation;
[0065] According to the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), degassed purified water + 0.3% SDS was used as the dissolution medium, the medium volume was 900 ml, the speed was 50 revolutions per minute, and samples were taken at 0 min, 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 90 min, and 120 min, respectively. The sampling volume was 5 ml each time, and the sample was filtered through a 10 μm primary filter membrane, and the filtrate was taken as the test solution;
[0066] Chromatographic detection conditions:
[0067] Chromatographic condition 1: injection volume 50 μl, other detection conditions remain unchanged;
[0068] Chromatographic condition 2: injection volume 20 μl, other detection conditions remain unchanged;
[0069] The results of the test under the above chromatographic conditions are as follows:
[0070] Injection volume 50μl: The test results show that the peak shape of the self-prepared test sample solution in water + 0.3% SDS medium is abnormal, see Figure 1 ;
[0071] Injection volume 20μl: The test results show that the peak shape of the self-prepared test solution in water + 0.3% SDS medium is still abnormal, see Figure 2 ;
[0072] Under the chromatographic conditions, the peak shape of the test solution in water + 0.3% SDS medium was abnormal. After the injection volume was modified, the peak shape was still abnormal. It was speculated that there was a solvent effect, that is, SDS as a surfactant had a negative impact on the dissolution behavior of the test solution, resulting in abnormal chromatographic peak shape. Therefore, SDS was not selected as the dissolution medium for the time being.
[0073] The graph of Example 3 shows that when water + 0.3% sodium dodecyl sulfate (SDS) is used as the dissolution medium, the peak shape of the test solution is abnormal, and the adjustment of the injection volume fails to improve this phenomenon. The results show that SDS as a surfactant is not suitable for the dissolution detection of vortioxetine hydrobromide tablets under the experimental conditions.
[0074] Embodiment 5
[0075] The dissolution medium was replaced with degassed purified water + 0.1% Tween 80, and the dissolution of the homemade preparation was tested;
[0076] According to the second method paddle method of the "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), 3 homemade preparations were used respectively, degassed purified water + 0.1% Tween 80 and degassed purified water + 0.3% Tween 80 were used as dissolution media, the medium volume was 900 ml, the speed was 50 revolutions per minute, and samples were taken at 0 min, 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 90 min, and 120 min, respectively. The sampling volume was 5 ml each time, and the sample was filtered through a 10 μm primary filter membrane, and the filtrate was taken as the test solution;
[0077] Chromatographic conditions: A chromatographic column with phenylsilane bonded silica as filler was used, the mobile phase was pH 4.5 ammonium acetate buffer-water-methanol (10:30:60), the detection wavelength was 226 nm, the column temperature was 40 °C, the flow rate was 1.0 ml / min, the injection volume was 50 μl, and the running time was 7 min;
[0078]
[0079] After adding Tween 80 to degassed purified water, the peak shape of the dissolution curve of the homemade preparation was improved at concentrations of 0.1% and 0.3%, as shown in Figure 2. Figure 3 and Figure 4However, there is still a jump point phenomenon. Even if different concentrations of Tween 80 are used, the dissolution curve still shows a certain degree of fluctuation, and the problem of the unevenness of the dissolution curve cannot be completely solved.
[0080] Embodiment 6
[0081] The dissolution medium was replaced with degassed purified water + 0.3% CTAB (hexadecyltrimethylammonium bromide) and degassed purified water + 0.1% CTAB to test the dissolution of the homemade preparations;
[0082] According to the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), 3 tablets of homemade preparations were used respectively, degassed purified water + 0.3% CTAB and degassed purified water + 0.1% CTAB were used as dissolution media, the medium volume was 900 ml, the rotation speed was 50 revolutions per minute, and samples were taken at 0 min, 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 90 min, and 120 min, respectively. The sampling volume was 5 ml each time, and the sample was filtered through a 10 μm primary filter membrane, and the filtrate was taken as the test solution;
[0083]
[0084] Using water + 0.3% CTAB and water + 0.1% CTAB as dissolution media, 3 homemade vortioxetine hydrobromide tablets were taken for measurement. There was no jump point phenomenon in the dissolution curve, the dissolution behavior was stable, the curve was smooth, and the peak shape was improved. Therefore, it is feasible to choose CTAB as a surfactant. In order to confirm the uniformity of the solution in the cup at each time point when using CTAB as a surfactant, the uniformity of the solution in the dissolution cup was investigated. Because the 10min and 15min RSD in the water + 0.3% CTAB medium were both greater than 10%, water + 0.1% CTAB was given priority.
[0085] Embodiment 7
[0086] Using a low concentration of surfactant, degassed purified water + 0.1% hexadecyltrimethylammonium bromide (CTAB) as the dissolution medium, take 3 tablets of the homemade preparation and test the uniformity of the solution in the cup at each time point for each homemade tablet;
[0087] According to the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), degassed purified water + 0.1% CTAB was used as the dissolution medium, the medium volume was 900 ml, the rotation speed was 50 revolutions per minute, and samples were taken at 0 min, 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 90 min, and 120 min, respectively. The sampling volume was 5 ml each time, and the sample was filtered through a 10 μm primary filter membrane, and the filtrate was taken as the test solution;
[0088]
[0089]
[0090] In the degassed purified water + 0.1% CTAB medium, the test results of 3 parallel dissolution solutions of 3 homemade tablets at different time points showed that the RSD of all samples was less than 2.0%, proving that the dissolution samples of homemade tablets in the degassed purified water + 0.1% CTAB medium were uniform. It was further confirmed that it was feasible to choose CTAB as a surfactant. In order to further optimize and confirm the appropriate CTAB concentration, the reference preparation was used to examine the effect of different concentrations of CTAB on the dissolution behavior.
[0091] Embodiment 8
[0092] Degassed purified water + 0.1% CTAB was used as the dissolution medium to test the dissolution of the reference preparation;
[0093] According to the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), degassed purified water + 0.1% CTAB was used as the dissolution medium, the medium volume was 900 ml, the rotation speed was 50 revolutions per minute, and samples were taken at 0 min, 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 90 min, and 120 min, respectively. The sampling volume was 5 ml each time, and the sample was filtered through a 10 μm primary filter membrane, and the filtrate was taken as the test solution;
[0094]
[0095] Using degassed purified water + 0.1% CTAB as the dissolution medium, the dissolution curve of the reference preparation of vortioxetine hydrobromide tablets had no jump point phenomenon, the dissolution behavior was stable, the curve was smooth, the RSD value of the dissolution data was low, and the dissolution behavior was consistent, indicating that the dissolution medium can provide a stable dissolution curve;
[0096] By using degassed purified water + 0.1% CTAB as the dissolution medium, the jump point phenomenon of the dissolution curve was effectively eliminated, ensuring the smoothness and stability of the dissolution curve. Using CTAB as a surfactant significantly improved the solubility of vortioxetine hydrobromide tablets in the aqueous medium, ensuring that the cumulative dissolution amount at each time point was stable, the curve was smooth, and the RSD value of the data was low. Using CTAB as the dissolution medium, the RSD value of the dissolution data was significantly reduced, the dissolution behavior was more consistent, and the accuracy and repeatability of the test results were ensured.
[0097] Embodiment 9
[0098] Degassed purified water + 0.01% CTAB was used as the dissolution medium to test the dissolution uniformity of multiple reference preparations in the cup;
[0099] According to the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), degassed purified water + 0.01% CTAB was used as the dissolution medium, the medium volume was 900 ml, the rotation speed was 50 revolutions per minute, and samples were taken at 5min, 10min, 15min, 20min, 30min, 45min, 60min, 90min, 120min, and 150min, respectively. The sampling volume was 5ml each time, and the sample was filtered through a 10μm primary filter membrane, and the filtrate was taken as the test solution;
[0100]
[0101]
[0102] In the water + 0.01% CTAB medium, the test results of three parallel dissolution solutions of three reference preparations at various time points showed that the RSD of the dissolution amount was less than 2.0%, proving that the dissolution samples of the reference preparations in the water + 0.01% CTAB medium had good uniformity. Therefore, the 0.01% CTAB concentration can meet the requirements for uniformity improvement. The dissolution curves of the six tablets were further investigated to see if there was a jump point problem.
[0103] Embodiment 10
[0104] Degassed purified water + 0.01% CTAB was used as the dissolution medium to test the dissolution of the reference preparation;
[0105] According to the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), degassed purified water + 0.01% CTAB was used as the dissolution medium, the medium volume was 900 ml, the rotation speed was 50 revolutions per minute, and samples were taken at 5min, 10min, 15min, 20min, 30min, 45min, 60min, 90min, 120min, and 150min, respectively. The sampling volume was 5ml each time, and the sample was filtered through a 10μm primary filter membrane, and the filtrate was taken as the test solution;
[0106]
[0107] Using degassed purified water + 0.01% CTAB as the dissolution medium, the dissolution curve of the reference preparation has no jump point phenomenon, the dissolution behavior is stable, the curve is smooth, the RSD value of the dissolution data is low, and the dissolution behavior is consistent, indicating that the dissolution medium can provide a stable dissolution curve;
[0108] Based on the experimental results of the above embodiments, the use of CTAB surfactant can improve the jump point phenomenon. Through the investigation of CTAB concentration, the reference preparation in degassed purified water
[0109] The homogeneity in the +0.01% CTAB medium was good, and the RSD was within 2%. Therefore, the final CTAB concentration was 0.01%.
[0110] The water medium for dissolution curve testing was finally determined to be: degassed purified water + 0.01% CTAB.
[0111] Embodiment 11
[0112] Degassed purified water + 0.01% CTAB was used as the dissolution medium to test the dissolution of the homemade preparation;
[0113] According to the second method paddle method of "Dissolution and Release Determination Method" (Chinese Pharmacopoeia 2020 Edition Part IV, General Rule 0931), degassed purified water + 0.01% CTAB was used as the dissolution medium, the medium volume was 900 ml, the rotation speed was 50 revolutions per minute, and samples were taken at 5min, 10min, 15min, 20min, 30min, 45min, 60min, 90min, 120min, and 150min, respectively. The sampling volume was 5ml each time, and the sample was filtered through a 10μm primary filter membrane, and the filtrate was taken as the test solution;
[0114]
[0115] Using degassed purified water + 0.01% CTAB as the dissolution medium, the dissolution curve of the homemade preparation has no jump point phenomenon, the dissolution behavior is stable, the curve is smooth, the RSD value of the dissolution data meets the requirements, and compared with the dissolution curve data of the reference preparation in Example 10, the data of 5min, 10min, 15min, and 30min are selected to calculate the similarity factor f2. The calculated result is 86.94, which is greater than 50, proving that the dissolution behavior of the homemade preparation is similar to that of the reference preparation and the quality is consistent. The fitting diagram of the dissolution curve of the reference preparation and the homemade preparation in water + 0.01% CTAB medium is shown in Figure 6 .
[0116] The technical features of the above embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.
[0117] The principles and implementation methods of the present invention are described in this article using specific examples. The description of the above embodiments is only used to help understand the method and core idea of the present invention. At the same time, for those skilled in the art, according to the idea of the present invention, there will be changes in the specific implementation methods and application scope. In summary, the content of this specification should not be understood as limiting the present invention.
Claims
1. An in vitro dissolution method for vortioxetine hydrobromide tablets, characterized in that: The specific steps of the dissolution detection of vortioxetine hydrobromide tablets include: (1) Take 1000 ml of degassed purified water, add 0.1 g of cetyltrimethylammonium bromide (CTAB) thereto, stir to fully dissolve, mix evenly, and obtain a water + 0.01% CTAB solution as a dissolution medium; (2) Take vortioxetine hydrobromide tablets and use the paddle method, with water + 0.01% CTAB as the dissolution medium, the medium volume is 900 ml, the rotation speed is 50 revolutions per minute, the medium temperature is 37.0°C, and samples are taken at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min in sequence. The sampling volume is 5 ml each time. The sample is filtered through a 10 μm primary filter membrane and the filtrate is taken as the test solution; Take about 13 mg of vortioxetine hydrobromide reference substance, accurately weigh it, put it in a 100 ml volumetric flask, add the mobile phase to dissolve and dilute to the scale, shake well, accurately measure 2 ml of the reference substance stock solution, put it in a 20 ml volumetric flask, add the dissolution medium to dilute to the scale, shake well, and the reference substance solution is obtained; (3) High performance liquid chromatography was used, with a chromatographic column filled with phenylsilane bonded silica gel, a mobile phase of pH 4.5 ammonium acetate buffer-water-methanol (10:30:60), a detection wavelength of 226 nm, a column temperature of 40°C, a flow rate of 1.0 ml / min, an injection volume of 50 μl, and a running time of 7 min. The cumulative dissolution amount at each time point was calculated, and the similarity factor f2 with the reference preparation was calculated, and f2 was greater than or equal to 50.
2. The method for preparing the dissolution curve of vortioxetine hydrobromide tablets according to claim 1, characterized in that: The vortioxetine hydrobromide tablets include a reference preparation of vortioxetine hydrobromide tablets and a homemade preparation, and the specifications of the vortioxetine hydrobromide tablets are all 10 mg.
3. The method for preparing the dissolution curve of vortioxetine hydrobromide tablets according to claim 1, characterized in that: Degassed purified water was used as the dissolution medium to test the dissolution performance.
4. The method for preparing the dissolution curve of vortioxetine hydrobromide tablets according to claim 1, characterized in that: The dissolution medium was replaced with degassed purified water + 0.3% sodium dodecyl sulfate (SDS), and the dissolution was tested.
5. The method for preparing the dissolution curve of vortioxetine hydrobromide tablets according to claim 1, characterized in that: The dissolution medium was replaced with water + 0.1% Tween 80, and the dissolution was tested.
6. The method for preparing the dissolution curve of vortioxetine hydrobromide tablets according to claim 1, characterized in that: The dissolution medium was replaced with water + 0.3% cetyltrimethylammonium bromide (CTAB), and the dissolution was tested.
7. The method for preparing the dissolution curve of vortioxetine hydrobromide tablets according to claim 6, characterized in that: Water + 0.1% CTAB was used as the dissolution medium to detect the dissolution.
8. The method for preparing the dissolution curve of vortioxetine hydrobromide tablets according to claim 1, characterized in that: Water + 0.01% CTAB was used as the dissolution medium to detect the dissolution.