Method for dissolving out ibuprofen sustained-release tablets

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a dissolution method of ibuprofen sustained-release tablets, which comprises the following steps: setting parameters by adopting a reciprocating cylinder dissolution device according to a dissolution rate method and dissolution standards in national drug standards of the ibuprofen sustained-release tablets of the State Drug Administration; the method comprises the following steps: putting an ibuprofen sustained-release tablet into an inner tube of a reciprocating barrel, reciprocating in a medium 1, continuously reciprocating in a medium 2 until an experiment is finished, and respectively sampling when the medium 1 and the medium 2 reciprocate; measuring a continuous filtrate obtained by sampling in the medium 1, adding a reagent for dilution, and uniformly shaking to obtain a test sample (1) and a test sample (2); and measuring the continuous filtrate obtained by sampling in the medium 2, adding another reagent, diluting and shaking uniformly to obtain a test sample (3) and a test sample (4). The RSD measured at the time point is obviously superior to that of the basket method on the basis that the result measured by the basket method is consistent with that measured by the basket method, reference is provided for quality and curative effect evaluation of refined bast fiber type imitated medicines, and support is provided for process improvement and enhancement.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and particularly relates to a dissolution method of a rofencodeine sustained-release tablet. Background Art

[0002] Dissolution testing is a key step in controlling drug absorption. The basket method and paddle method were the first to be widely used as quality control methods, but there are certain limitations due to the differences in the volume of the dissolution medium, the dissolution apparatus, the fluid dynamic characteristics, and the physiological environment in vivo. The study of the reciprocating cylinder method can be traced back to the 1970s, when it was proposed by Professor Amold Beckett of the University of London. At present, the United States Pharmacopeia (USP), the British Pharmacopoeia (BP), and the European Pharmacopoeia (EP) all include the reciprocating cylinder method in addition to the basket method and the paddle method. The 2020 edition of the Pharmacopoeia of the People's Republic of China (ChP) also added the reciprocating cylinder method in the general principles of dissolution and release determination. Compared with the traditional basket method and paddle method, the reciprocating cylinder method has great flexibility in the composition of the dissolution medium. It can not only perform multi-point sampling in a single row of dissolution cups, but also move the reciprocating cylinder from one dissolution cup to the next dissolution cup, and each dissolution cup can be filled with different media. In addition, the reciprocating cylinder method also has unique fluid dynamics advantages. It relies on the solid-liquid shear force of the vertical movement of the reciprocating cylinder loaded with drugs to achieve drug dissolution, and can provide medium conditions that are closer to the complex physiological environment changes of human gastrointestinal peristalsis. The speed is milder than the paddle basket dissolution method, and it has a strong ability to distinguish dissolution behavior. In recent years, the reciprocating cylinder method has been used more and more in drug research. The reciprocating cylinder method has been used for dissolution determination of varieties such as lithium carbonate sustained-release tablets, fluoxetine delayed-release capsules, and nifedipine sustained-release tablets.

[0003] The present invention selects fenpropenza sustained-release tablets as the research object. The fenpropenza sustained-release tablets are a double-layer compound preparation made of ibuprofen and codeine phosphate. Ibuprofen is an anti-inflammatory analgesic, which has an analgesic effect on the homologous inflammatory tissue by inhibiting cyclooxygenase, and codeine phosphate is a central analgesic. The two exert an analgesic synergistic effect through different mechanisms of action and optimal ratio composition. At present, the current quality standard dissolution test method for this variety is the basket method, that is, dissolving in a hydrochloric acid solution for 20 minutes to examine the solubility of codeine phosphate, and then replacing the dissolution medium with a phosphate buffer (pH7.2) to continue to examine the solubility of ibuprofen. This dissolution method requires the operator to manually stop the machine at the time point to replace the dissolution medium, which is time-consuming; the fenpropenza sustained-release tablets in the rotating basket will continue to dissolve due to wetting, so that the relative standard deviation (Relative standard deviation; RSD) of each subsequent point of ibuprofen fluctuates greatly, and the RSD is above 10%, which cannot better guarantee the product quality. In view of this, the present invention adopts the reciprocating cylinder method, refers to the dissolution method and dissolution standard in the national drug standard of levofloxacin sustained-release tablets, compares the dissolution and precision with the basket method, determines the dissolution conditions of the reciprocating cylinder method, and establishes a new method for dissolution determination of levofloxacin sustained-release tablets by the reciprocating cylinder method, hoping to provide a basis for the quality evaluation of this product and its inclusion in the pharmacopoeia, and provide support for process improvement and enhancement. Summary of the invention

[0004] The purpose of the present invention is to provide a dissolution method for levofloxacin sustained-release tablets. A reciprocating cylinder dissolution tester is used to investigate factors such as the reciprocating frequency and the specifications of the screen. The RSD measured at the time point is significantly better than that of the basket method on the basis of the consistency of the results measured by the basket method. This provides a reference for the quality and efficacy evaluation of generic hemp drugs and provides support for process improvement and enhancement.

[0005] The objective of the present invention is achieved through the following technical solutions:

[0006] The present invention provides a dissolution method of a rofencodeine sustained-release tablet, comprising the following steps:

[0007] (1) Referring to the dissolution method and dissolution standard in the National Drug Standard WS1-(X-214)-2004Z-2021 of the State Food and Drug Administration for Profencocet Sustained-Release Tablets, a reciprocating cylinder dissolution apparatus was used and parameters were set;

[0008] (2) Place a sustained-release tablet of fenpropiprofen in the inner tube of the reciprocating cylinder, reciprocate in medium 1, and then continue to reciprocate in medium 2 until the end of the experiment, and take samples when medium 1 and medium 2 are reciprocating;

[0009] (3) Measure the filtrate obtained by sampling in medium 1, add a reagent to dilute and shake well, and use them as test sample (1) and test sample (2); measure the filtrate obtained by sampling in medium 2, add another reagent to dilute and shake well, and use them as test sample (3) and test sample (4).

[0010] Furthermore, in step (1), the parameters include a water bath temperature of 37±0.5°C, a volume of medium 1 and medium 2 of 250 mL, a reciprocating stroke of 10 cm, a dripping time of 10 s, an immersion time of 15 s, a reciprocating frequency of 7 dpm, and a sieve condition of no upper sieve and a lower sieve of 40 mesh.

[0011] Furthermore, in step (2), the sampling during the reciprocating in medium 1 is 10 mL at 20 min and 120 min respectively; the sampling during the reciprocating in medium 2 is 10 mL at 2 h and 4 h respectively.

[0012] Further, in step (3), the specific preparation method of the test sample (1) and the test sample (2) is to measure 5 mL of the 20-min and 120-min filtrates in medium 1, respectively, put them in a 20-mL volumetric flask, add 0.3 mL of potassium hydroxide test solution, dilute to the scale with a phosphate buffer having a pH of 7.2, and shake well. The specific preparation method of the test sample (3) and the test sample (4) is to measure 5 mL of the 2-h and 4-h filtrates in medium 2, respectively, put them in a 20-mL volumetric flask, dilute to the scale with a phosphate buffer having a pH of 7.2, and shake well.

[0013] The beneficial effects of the present invention are:

[0014] The present invention investigates the dissolution of samples in acidic dissolution media and buffer dissolution media, simulating the different residence times and pH environmental changes of sustained-release preparations in the gastrointestinal tract. Compared with the basket method, the operator does not need to manually stop the machine to change the dissolution medium at a time point, and the reciprocating cylinder can be automatically moved from one dissolution cup to the next dissolution cup of a different medium, saving time and facilitating operation; in addition, the rofencodeine sustained-release tablets in the rotating basket will not continue to dissolve due to wetting, and there is almost no fluid dynamics dead angle, which affects the stability and accuracy of the dissolution results. The dissolution method can more truly reflect the release characteristics of the product and better predict the drug release in vivo. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The high performance liquid chromatogram of the present invention, wherein A: hydrochloric acid solution; B: phosphate buffer (pH 7.2). DETAILED DESCRIPTION

[0016] Example 1

[0017] 1. Instruments and reagents

[0018] 1.1 Instrument

[0019] SYSTEM ADR III-7 reciprocating cylinder dissolution apparatus (Logan Instruments, USA); Sotax AT.7X drug dissolution apparatus (Sotax, Switzerland); SYSTEM 860DLA dissolution apparatus (Logan Instruments, USA); high performance liquid chromatograph (Waters e2695, USA); XPR36 electronic analytical balance (Mettler-Toledo, Switzerland); ZKT18F vacuum degasser (TianDa TianFa Technology Co., Ltd.).

[0020] 1.2 Drug testing

[0021] Codeine profenoflavone sustained-release tablets (Southwest Pharmaceutical Co., Ltd., batch number: 230815, 230816, 230817, specification: compound); codeine phosphate reference substance (China Food and Drug Inspection Institute, batch number: 171203-201808); ibuprofen reference substance (China Food and Drug Inspection Institute, batch number: 100179-202308); methanol and tetrahydrofuran were of chromatographic grade; triethylamine, hydrochloric acid, potassium dihydrogen phosphate, sodium hydroxide, and potassium hydroxide were of analytical grade; water was homemade purified water.

[0022] 2 Methods and Results

[0023] 2.1 Chromatographic conditions

[0024] Chromatographic column: Agilent XDB-C18 (250mm×4.6mm, 5μm); mobile phase: 0.05mol / L potassium dihydrogen phosphate buffer (pH adjusted to 6.0 with triethylamine)-methanol-tetrahydrofuran (100:160:10, V / V / V); flow rate: 1.0mL / min; detection wavelength: 254nm; column temperature: 40℃; injection volume: 20μL.

[0025] 2.2 Solution preparation

[0026] Dissolution medium: Take 24 mL of dilute hydrochloric acid, dilute to 1000 mL with water, shake well to obtain hydrochloric acid solution; take 50 mL of 0.2 mol / L potassium dihydrogen phosphate solution and 35 mL of 0.2 mol / L sodium hydroxide solution, add freshly boiled cold water to dilute to 200 mL, shake well to obtain phosphate buffer solution (pH 7.2). These are respectively called medium 1 and medium 2.

[0027] Reference solution: Accurately weigh appropriate amounts of codeine phosphate and ibuprofen reference substances, dissolve them in phosphate buffer (pH 7.2) to prepare a reference solution containing approximately 13 μg of codeine phosphate and 200 μg of ibuprofen per 1 mT.

[0028] 2.3 Dissolution test method

[0029] Referring to the dissolution method and dissolution standard in the National Drug Standard WS1-(X-214)-2004Z-2021 of the State Food and Drug Administration for lofencodeine sustained-release tablets, a reciprocating cylinder dissolution apparatus was used, the water bath temperature was set to (37±0.5)°C, the volume of media 1 and 2 were both 250 mL, the reciprocating stroke was 10 cm, the dripping time was 10 s, the immersion time was 15 s, the reciprocating frequency was 7 dpm, the sieve conditions were no upper sieve, and the lower sieve was 40 mesh. Six lofencodeine sustained-release tablets were placed in the inner tube of the reciprocating cylinder, and reciprocated in the 6th row of medium 1. 10 mL was sampled at 20 and 120 min, respectively; after 2 h, it was automatically moved to the 1st row, and continued to reciprocate in medium 2 until the end of the experiment. 10 mL was sampled at 2 and 4 h, respectively, filtered, and the filtrate was taken.

[0030] Accurately measure 5 mL of the filtrate at 20 and 120 min in medium 1, place it in a 20 mL volumetric flask, add 0.3 mL of potassium hydroxide test solution, dilute to the mark with phosphate buffer (pH 7.2), shake well, and use as the test sample (1)(2). Accurately measure 5 mL of the filtrate at 2 and 4 h in medium 2, place it in a 20 mL volumetric flask, dilute to the mark with phosphate buffer (pH 7.2), shake well, and use as the test sample (3)(4).

[0031] 2.4 Methodological Review

[0032] 2.4.1 Specificity Investigation

[0033] Weigh the blank excipients according to the prescription ratio, dissolve and dilute them with medium 1 and medium 2 to prepare blank excipient hydrochloric acid solution and blank excipient phosphate buffer (pH 7.2); take appropriate amounts of mobile phase under 2.1, reference solution under 2.2, and dissolution medium 1 and medium 2, and measure according to the chromatographic conditions under 2.1, and record the chromatogram ( Figure 1 The results showed that the mobile phase, medium 1, medium 2, blank auxiliary hydrochloric acid solution and blank auxiliary phosphate buffer (pH 7.2) had no interfering peaks at the retention time of the reference solution, indicating that the method had strong specificity.

[0034] 2.4.2 Limit of quantification and detection limit

[0035] Accurately measure the appropriate amount of codeine phosphate and ibuprofen reference stock solutions under 2.2, dilute them with phosphate buffer (pH 7.2) to prepare codeine phosphate reference solution and ibuprofen reference solution, measure them according to the chromatographic conditions under 2.1, and record the peak area. Further, accurately measure the appropriate amount of the above solutions, dilute them to the scale with phosphate buffer (pH 7.2), and measure them according to the chromatographic conditions under 2.1. The quantification limit of codeine phosphate was 63.44 ng / ml (S / N = 9.799), and the detection limit was 31.72 ng / ml (S / N = 2.71); the quantification limit of ibuprofen was 0.508 μg / ml (S / N = 10.82), and the detection limit was 0.152 μg / ml (S / N = 3.15).

[0036] 2.4.3 Investigation of linear relationship

[0037] Accurately measure appropriate amounts of codeine phosphate and ibuprofen reference stock solutions under 2.2, dilute with phosphate buffer (pH 7.2) to prepare a series of reference solutions, and measure according to the chromatographic conditions under 2.1, and record the peak area. Linear regression was performed with codeine phosphate and ibuprofen mass concentration (C, μg / mL) as the abscissa and peak area (A) as the ordinate, respectively, to obtain the regression equations of codeine phosphate and ibuprofen A1 = 4417.33C1-44.79 (r = 0.99999), A2 = 1213.52C2 + 409.47 (r = 0.99999). The results show that in phosphate buffer (pH 7.2), the codeine phosphate mass concentration is in the range of 0.06344 to 25.3762 μg / mL, and the ibuprofen mass concentration is in the range of 0.5075 to 406.03356 μg / mL, both of which have a good linear relationship with the peak area.

[0038] 2.4.4 Precision investigation

[0039] Take an appropriate amount of the reference solution under 2.2, and inject it continuously for 5 times according to the chromatographic conditions under 2.1, and record the peak area. The calculated RSD results are 0.06% and 0.09% (n=5), respectively, indicating that the instrument has good precision.

[0040] 2.4.5 Accuracy

[0041] Weigh appropriate amount of prescription excipients, accurately measure 2, 2 and 3 mL of reference substance stock solution under 2.2, respectively, and prepare test solutions with 10%, 100% and 150% concentration levels using medium 1 and medium 2, respectively. Prepare 3 copies of each concentration in parallel. Determine according to the chromatographic conditions under 2.1 and record the peak area. Calculate the recovery rate. In medium 1, the average recovery rates of codeine phosphate at 10%, 100% and 150% concentration levels were 97.7%, 102.8% and 102.9%, respectively, with RSDs of 1.0%, 0.3% and 0.4%, respectively; the average recovery rates of ibuprofen were 98.2%, 99.1% and 99.0%, respectively, with RSDs of 0.6%, 0.3% and 0.1%, respectively. In medium 2, the average recoveries of codeine phosphate at 10%, 100% and 150% concentration levels were 100.9%, 102.8% and 103.4%, with RSDs of 1.6%, 0.8% and 0.2%, respectively; the average recoveries of ibuprofen were 100.4%, 98.6% and 99.7%, with RSDs of 0.1%, 1.4% and 0.8%, respectively, indicating that the method has high accuracy.

[0042] 2.4.6 Repeatability

[0043] Prepare 6 test sample solutions according to 2.3, measure according to the chromatographic conditions in 2.1, and record the chromatograms. The results show that the RSD of dissolution at 20 and 120 min in medium 1 and 2 and 4 h in medium 2 are 0.81%, 2.12%, 2.18%, and 2.69%, respectively, indicating good repeatability.

[0044] 2.4.7 Solution stability test

[0045] Take the control solution under 2.2 and the 20min and 4h test solution, place them at room temperature for 0, 9, 15, 24, 36, and 48h, respectively, and measure them according to the chromatographic conditions under 2.1, and record the peak area. Compared with 0h, the peak area ratios of codeine phosphate in the control solution at 9, 15, 24, 36, and 48h are 100.0%, 99.9%, 99.7%, 99.9%, and 99.8%, respectively, and the RSDs are 0.00%, 0.14%, 0.043%, 0.055%, and 0.087%, respectively; the peak area ratios of ibuprofen in the control solution are 100.0%, 99.9%, 100.0%, 100.0%, and 100.0%, respectively, and the RSDs are 0.00%, 0.046%, 0.070%, 0.034%, respectively. %, 0.049%; 20min codeine phosphate peak area ratios were 100.0%, 100.1%, 100.1%, 100.0%, 100.3%, and RSDs were 0.00%, 0.14%, 0.14%, 0.12%, 0.30%, respectively; 4h ibuprofen peak area ratios were 99.9%, 99.8%, 100.1%, 100.0%, 100.1%, and RSDs were 0.067%, 0.11%, 0.085%, 0.11%, 0.048% (n=6), respectively. This indicates that the control solution and the test solution have good stability within 48h at room temperature.

[0046] 2.5 Investigation of reciprocating frequency

[0047] Unlike the paddle basket dissolution, which relies on the stirring of the liquid flow caused by the rotation of the rotating shaft to dissolve the drug, the reciprocating cylinder dissolution relies on the solid-liquid shear force of the vertical reciprocating motion of the reciprocating cylinder loaded with the drug to dissolve the drug. Therefore, the reciprocating frequency (Dipper minute; dpm) is an important parameter that affects the dissolution and release of the drug in the reciprocating cylinder dissolution. The present invention adopts reciprocating frequencies of 10, 13, 15, and 20 dpm, respectively, and the mesh sizes of the upper and lower sieves are set to 40 meshes. The dissolution of fentanyl sustained-release tablets in medium 1 and medium 2 is investigated, and compared with the basket dissolution results, see Table 1. The results show that as the reciprocating frequency increases, the solubility gradually increases. Compared with the basket method, the solubility at each time is low when the reciprocating frequency is 10 and 13 dpm; when the reciprocating frequency is 20 dpm, the solubility in medium 2 is high. When the reciprocating frequency is 15dpm, it is similar to the dissolution result of the basket method, and the RSD at each time point is small; further, the dissolution of different batches of fencocidin sustained-release tablets is determined under the conditions of a reciprocating frequency of 15dpm and an upper and lower screen of 40 meshes. As shown in Table 2, the ibuprofen dissolution of 230816 batches and 230817 batches of fencocidin sustained-release tablets in medium 2 is significantly lower than that of 230815 batches, and the RSD is large, indicating that the reciprocating frequency is 15dpm, and the dissolution conditions of the upper and lower screens of 40 meshes are not suitable for the dissolution determination of fencocidin sustained-release tablets in the reciprocating cylinder device. In addition, under this condition, the reciprocating cylinder has a phenomenon of unsmooth medium exchange in the reciprocating cylinder during the reciprocating process, which affects the dissolution rate of fencocidin sustained-release tablets. Therefore, the conditions of the screen specifications need to be further investigated.

[0048] Table 1 Comparison of dissolution and RSD of fenpropipro sustained-release tablets with different reciprocating frequencies (upper and lower sieves 40 mesh)

[0049]

[0050] Table 2 Comparison of dissolution and RSD of different batches of profenofenadine sustained-release tablets in medium 2 (15 dpm, upper and lower sieves 40 mesh)

[0051]

[0052] 2.6 Screen Specifications

[0053] The mesh specifications of the reciprocating cylinder dissolution test device are generally 8 to 400 meshes, the commonly used mesh number of the lower screen is 20 to 40 meshes, and the upper screen specifications are generally 20 to 100 meshes or some varieties are not added with a screen. The present invention examines the upper screen of 80 mesh and the lower screen of 40 mesh under the condition of a reciprocating frequency of 15 dpm; the upper and lower screens are 40 meshes; no upper screen, the lower screen is 40 mesh; no upper screen, the lower screen is 80 mesh. As shown in Table 3, with the increase of the mesh number of the upper screen, the mesh aperture decreases, the shear force formed by the medium on the surface of the preparation decreases, and the medium in the cylinder cannot be exchanged quickly, so that the dissolution of ibuprofen in medium 2 gradually decreases, and the RSD gradually increases. When the upper screen is 80 mesh, it has a significant effect on the release of ibuprofen. The lower screen has a smaller effect. Therefore, the present invention considers that the water inside and outside the cylinder can be exchanged quickly, smoothly and completely during the up and down operation of the reciprocating cylinder, and selects no upper screen and a lower screen of 40 mesh.

[0054] Table 3 Comparison of dissolution and RSD of fenpropipro sustained-release tablets with different mesh specifications (15 dpm)

[0055]

[0056] 2.7 Determination of dissolution conditions by reciprocating cylinder method

[0057] By the investigation of the above-mentioned reciprocating frequency and screen specifications, it is determined that there is no upper screen and the screen condition of 40 meshes of the lower screen. In combination with the screen condition, the present invention selects the reciprocating frequency of 7, 12, and 15dpm to compare with the basket method dissolution result, so as to determine the reciprocating cylinder method dissolution condition. As shown in Table 4, the result shows that the dissolution of 7dpm reciprocating frequency is more similar to the basket method dissolution, and RSD is also relatively small. In addition, by different batches of different brands of dissolution apparatus, the dissolution determination of fenhezidofen sustained-release tablets is carried out, as shown in Table 5, the reciprocating cylinder method dissolution results of different batches of fenhezidofen sustained-release tablets are similar to the results obtained by the basket method of different brands of dissolution apparatus, and there is no abnormality, and the reciprocating cylinder method RSD is lower than the basket method, and the precision is better, indicating that the reciprocating cylinder dissolution condition is 7dpm reciprocating frequency, no upper screen, and 40 meshes of the lower screen can meet the experimental requirements.

[0058] Table 4 Comparison of dissolution and RSD of fenpropipro sustained-release tablets with different reciprocating frequencies (without upper sieve, lower sieve 40 mesh)

[0059]

[0060] Table 5 Comparison of dissolution and RSD of different batches of fenpropipro sustained-release tablets (7dpm, no upper sieve, lower sieve 40 mesh)

[0061]

[0062] in conclusion

[0063] Compared with the traditional pulp basket method, the reciprocating cylinder method has the flexibility to change the medium, shortens the time of changing the medium, conforms to the physiological environment of the human body, and has a strong ability to distinguish the dissolution behavior of the preparation. However, compared with the basket method and pulp method, the volume of dissolution medium required for the reciprocating cylinder method is smaller, and the excessive peak area / tailing will affect the dissolution results when performing liquid phase analysis on drugs with larger specifications. The present invention dilutes the test solution to reduce the injection concentration. Secondly, the reciprocating frequency is the number of reciprocations per minute of the glass cylinder loaded with the preparation in the dissolution cup, which reflects the changes in different fluid dynamics. Different reciprocating frequencies may have an impact on the in vitro dissolution of the drug. At present, the reciprocating frequency of the reciprocating cylinder dissolution method of the varieties included in the "United States Pharmacopoeia" is generally stipulated to be 6 to 30 dpm. Generally, when the reciprocating frequency is 10 to 20 dpm, it is more suitable for simulating human physiological conditions. The present invention, when the upper and lower screens are 40 meshes, investigates the dissolution change of the fenoxamine sustained-release tablets under the conditions of reciprocating frequency of 10, 13, 15, and 20 dpm, and the results show that as the reciprocating frequency is accelerated, the dissolution rate gradually increases. However, the phenomenon of unsmooth medium exchange in the reciprocating cylinder occurs during the dissolution process, which may be caused by the obstruction of the screen aperture, resulting in a significant reduction in the dissolution rate of the fenoxamine sustained-release tablets, and the dissolution results are unstable. Combined with the test process dissolution phenomenon and the screen conditions, the reciprocating frequency is further investigated, and it is finally determined that the reciprocating cylinder dissolution device measures the key parameters as follows: a reciprocating frequency of 7 dpm, no upper screen, and a lower mesh number of 40 meshes.

[0064] This method examines the dissolution of samples in acidic dissolution media and buffer dissolution media, simulating the different residence times and pH environment changes of sustained-release preparations in the gastrointestinal tract. Compared with the basket method, the operator does not need to manually stop the machine to change the dissolution medium at a certain time. The reciprocating cylinder can automatically move from one dissolution cup to the next dissolution cup with a different medium, saving time and facilitating operation. In addition, the sustained-release tablets of lofenac in the rotating basket will not continue to dissolve due to wetting, and there are almost no fluid dynamic dead angles that affect the stability and accuracy of the dissolution results. This dissolution method can more truly reflect the release characteristics of this product and better predict the drug release in vivo.

[0065] In summary: The present invention adopts a reciprocating cylinder dissolution test device to investigate factors such as reciprocating frequency and screen specifications, and establishes a new method for improving the release precision and convenience of rofencodeine sustained-release tablets. And based on the consistent results with the basket method, the RSD measured at the time point is significantly better than the basket method, which provides a reference for the quality and efficacy evaluation of hemp-like generic drugs and provides support for process improvement and improvement.

[0066] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution of the present invention, which should be covered by the scope of the claims of the present invention.

Claims

1. A dissolution method for a profenoflavone sustained-release tablet, characterized in that: The following steps are involved: (1) Refer to the dissolution method and dissolution standard in the National Drug Standard WS1-(X-214)-2004Z-2021 of the State Food and Drug Administration for Profencoline Sustained-Release Tablets, use a reciprocating cylinder dissolution apparatus, and set the parameters; (2) Place a sustained-release tablet of fenpropiprofen in the inner tube of the reciprocating cylinder, reciprocate in medium 1, and then continue to reciprocate in medium 2 until the end of the experiment, and take samples when medium 1 and medium 2 are reciprocating; (3) Take a measure of the filtrate obtained from the sample in medium 1, dilute it with a reagent and shake it well to obtain the sample (1) and the sample (2); take a measure of the filtrate obtained from the sample in medium 2, dilute it with another reagent and shake it well to obtain the sample (3) and the sample (4).

2. The dissolution method of the profencodeine sustained-release tablets as claimed in claim 1, characterized in that: In step (1), the parameters include a water bath temperature of 37±0.5°C, a volume of medium 1 and medium 2 of 250 mL, a reciprocating stroke of 10 cm, a dripping time of 10 s, an immersion time of 15 s, a reciprocating frequency of 7 dpm, and a sieve condition of no upper sieve and a lower sieve of 40 mesh.

3. The dissolution method of the profencodeine sustained-release tablets as claimed in claim 1, characterized in that: In step (2), the sampling during the reciprocating in medium 1 is 10 mL at 20 min and 120 min respectively; the sampling during the reciprocating in medium 2 is 10 mL at 2 h and 4 h respectively.

4. The preparation method according to claim 1, characterized in that: In step (3), the specific preparation method of the test sample (1) and the test sample (2) is to measure 5 mL of the 20-min and 120-min filtrates in medium 1, respectively, place them in a 20-mL volumetric flask, add 0.3 mL of potassium hydroxide test solution, dilute to the scale with a phosphate buffer solution of pH 7.2, and shake well. The specific preparation method of the test sample (3) and the test sample (4) is to measure 5 mL of the 2-h and 4-h filtrates in medium 2, respectively, place them in a 20-mL volumetric flask, dilute to the scale with a phosphate buffer solution of pH 7.2, and shake well.

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