CN112526055A - Method for determining in-vitro dissolution of felodipine sustained-release tablets - Google Patents
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Abstract
The invention belongs to the technical field of pharmaceutical analysis, and discloses a method for determining in-vitro dissolution of felodipine sustained-release tablets, which comprises the steps of dissolving the felodipine sustained-release tablets by using a two-chamber model experimental device, wherein a dissolution medium is 0.3% of sodium dodecyl sulfate phosphate buffer solution with pH 6.8, placing the felodipine sustained-release tablets in a rotating basket, the rotating speed of the rotating basket is 100 rpm, filtering the dissolution liquid by a filter membrane, continuously extracting the dissolution liquid, and determining the concentration of felodipine in the dissolution liquid at the extraction speed of the dissolution liquid and the supplement speed of the dissolution medium of 5-12 mL/min until the felodipine sustained-release tablets are completely dissolved; and (3) measuring the average dissolution concentration of the felodipine in the dissolution liquid at different time points by adopting a high performance liquid phase. The in vitro dissolution method ensures the accuracy of in vitro dissolution experiments by simulating in vivo absorption processes, realizes the consistency of dissolution curves measured by the in vitro dissolution experiments and in vivo absorption processes, and provides guarantee for realizing good prediction of human body bioequivalence.
Description
Technical Field
The invention relates to the technical field of pharmaceutical analysis, in particular to a method for determining in-vitro dissolution of felodipine sustained-release tablets.
Background
At present, in-vitro dissolution experiments are considered to BE capable of estimating in-vivo dissolution behaviors and absorption conditions, but the in-vivo environment is complex, so that the phenomenon that the dissolution of preparation intermediates out of the body is similar and BE in the body is not equivalent is easily caused, the research and development progress of enterprises is hindered, and economic burden is also brought.
Felodipine, chemical name 2, 6-dimethyl-4- (2, 3-dichlorophenyl) -1, 4-dihydro-3, 5-pyridinedicarboxylic acid methyl ethyl ester, molecular formula C18H19Cl2NO4Is a selective calcium ion antagonist and has better antihypertensive effect. The mechanism of lowering blood pressure of felodipine is mainly to inhibit the inflow of extracellular calcium of arteriolar smooth muscle, selectively dilate arteriolar, and has no direct effect on myocardial contractility and cardiac conduction in the therapeutic dose range, and has no influence on the tension of venous smooth muscle and epinephrine blood vessel, so orthostatic hypotension is not easy to cause. Meanwhile, the felodipine has low price and high safety, so that the felodipine becomes one of the most commonly used antihypertensive drugs. Felodipine, a member of many poorly soluble drugs, also has problems of low bioavailability and an adverse effect on drug efficacy due to low solubility.
The conventional dissolution mode is a basket method or a slurry method, has a plurality of defects in structure and performance, and cannot comprehensively simulate the dissolution/absorption process of the medicine in vivo, so that the dissolution test is only used as a quality means for controlling the medicine in vitro and cannot be associated with the actual situation in vivo. The traditional dissolution method is a closed dissolution system mode, and physiological conditions such as gastrointestinal tract peristalsis, fluid dynamics and the like in vivo cannot be simulated; if the medium volume and the type of the dissolution medium are unreasonable, the dissolution medium is easy to be inconsistent with the in vivo situation, and the differentiation degree of the dissolution of the pharmaceutical preparation is not obvious enough, so that the actual dissolution behavior in vivo cannot be truly reflected. Based on felodipine with different dosage forms and different specifications, in the in-vitro dissolution process, a proper method needs to be selected in order to properly simulate the dissolution/absorption mechanism of the drug and provide reference for well predicting the bioequivalence of a human body.
The Chinese patent application CN201510155510.0 discloses a felodipine sustained-release tablet and a preparation process thereof, the quality detection experiment of the felodipine tablet is carried out, a pulp-plate method is adopted for dissolution rate detection, the actual dissolution behavior in vivo cannot be truly reflected, and the preparation method has certain limitation.
Therefore, the development of an in vitro dissolution method that simulates in vivo absorption is of great significance to pharmaceutical companies.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide a method for measuring the in vitro dissolution of the felodipine sustained-release tablet, which measures the dissolution concentration of the felodipine sustained-release tablet by simulating the dynamic continuous process of in vivo dissolution and absorption so as to realize good prediction of the bioequivalence of a human body.
In order to achieve the purpose, the invention adopts the following technical scheme:
on one hand, the invention provides a method for determining in-vitro dissolution of felodipine sustained-release tablets, which is to perform dissolution on the felodipine sustained-release tablets by using a two-chamber model experimental device for simulating in-vivo dissolution and transmembrane absorption processes of insoluble oral pharmaceutical preparations, and comprises the following specific steps:
1) dissolving media enter the porous filter membrane cup through the action of the liquid inlet pump, when the volumes of the dissolving media in the porous filter membrane cup and the dissolving cup in the outer chamber are the same, the liquid outlet pump is started, the working frequencies of the liquid inlet pump and the liquid outlet pump are consistent, and the total volume of the dissolving media is kept unchanged; the dissolution medium is 0.1-0.5% lauryl sodium sulfate phosphate buffer solution with the pH value of 6.8, and the aperture of the filter membrane coated outside the porous filter membrane cup is 0.45 mu m;
2) placing the felodipine sustained-release tablets in a rotating basket, wherein the rotating speed of the rotating basket is 50-300 rpm, filtering the dissolution liquid by a filter membrane, continuously extracting the dissolution liquid, wherein the extraction speed of the dissolution liquid and the supplement speed of a dissolution medium are both 5-12 mL/min, and measuring the concentration of felodipine in the dissolution liquid at a fixed time point until the felodipine sustained-release tablets are completely dissolved;
3) and (3) measuring the average dissolution concentration of felodipine at different time points in the dissolution liquid by adopting a high-performance liquid phase, obtaining an average differential dissolution curve graph between the average dissolution concentration and the dissolution time of felodipine according to the corresponding time points and the average dissolution concentration of felodipine, and obtaining an accumulated dissolution curve graph between the accumulated dissolution mass fraction and the dissolution time according to the differential dissolution relation.
Further, the dissolution medium is 0.1%, 0.15%, 0.2%, 0.3%, 0.5% sodium dodecyl sulfate in pH 6.8 phosphate buffer. Wherein the 0.1-0.5% sodium dodecyl sulfate pH 6.8 phosphate buffer solution is 1000 mL phosphate buffer solution containing 1-5 g sodium dodecyl sulfate. Experiments prove that the in vitro dissolution curve obtained by using a proper dissolution medium to perform in vitro dissolution experiments has better discrimination, can appropriately discriminate the quality and the process difference of a tested preparation and a reference preparation, has high stability, meets the requirements, and has reproducible determination results when the dissolution curve is determined.
Further, the concentration of felodipine in the dissolution liquid is determined by adopting a high performance liquid chromatography, and the specific process comprises the following steps: after the dissolution liquid is subjected to centrifugal treatment, precisely measuring 20 mu L of the dissolution liquid, injecting the solution into a high performance liquid chromatograph, recording a chromatogram, and calculating the concentration of the corresponding felodipine; the centrifugal treatment conditions are as follows: rotor No. 2, 4000rpm, 5 min.
Further, the chromatographic conditions of the high performance liquid chromatography are as follows: c18 (20-H046); mobile phase: methanol-acetonitrile-ultrapure water = volume ratio (5: 3: 2); flow rate: 1 mL/min; wavelength: 238 nm; sample introduction amount: 20 mu L of the solution; column temperature: 35 ℃ is carried out.
According to the differential dissolution data of the felodipine sustained-release tablets, the calculation formula for obtaining the cumulative dissolution relation between the cumulative dissolution fraction and the dissolution time is as follows:
wherein, FdisIs the reference formulation or the test formulation at tiCumulative dissolution mass fraction at time, n is total number of samples, i is an integer between 1 and n, tiDissolution time, t, for the ith dissolution samplei-1Dissolution time corresponding to the i-1 th dissolution sample, CiConcentration of the i-th dissolution sample, Ci-1The concentration of the i-1 th dissolution sample, the Flowrate the flow rate of the vehicle and the dose of the pharmaceutical formulation.
Further, the felodipine sustained-release tablets comprise reference preparations and tested preparations, a similarity factor f2 is calculated by using average dissolution concentration data of the reference preparations and the tested preparations of the felodipine sustained-release tablets by using a similarity factor method, and the similarity factor f2 is used for comparing the similarity of dissolution curves of the reference preparations and the tested preparations of the felodipine sustained-release tablets; when the similarity is judged by using the value of the similarity factor f2, when the similarity factor f2 is greater than or equal to 50, the dissolution curves of the reference preparation and the tested preparation of the felodipine sustained-release tablet are similar, and when the similarity factor f2 is less than 50, the dissolution curves of the reference preparation and the tested preparation of the felodipine sustained-release tablet are not similar.
And according to the accumulative dissolution relation of the reference preparation and the accumulative dissolution relation of the tested preparation, obtaining a calculation formula of a similarity factor between the accumulative dissolution relation of the reference preparation and the accumulative dissolution relation of the tested preparation, wherein the calculation formula comprises the following steps:
wherein f is2 TIs a similarity factor between the cumulative dissolution relation of the reference preparation and the cumulative dissolution relation of the tested preparation, n is the total sampling number, i is an integer between 1 and n, FTdisIs the cumulative dissolution mass fraction of the test preparation at the dissolution time corresponding to the i-th dissolution sample, FRdisThe cumulative dissolution mass fraction of the reference preparation at the dissolution time corresponding to the i-th dissolution sample is used.
Further, the temperature of the dissolution medium is controlled at (37. + -. 0.5) DEG C. Experiments prove that the temperature of the dissolution medium enables felodipine to have higher stability, and simultaneously, the temperature in a human body can be simulated, and the measured dissolution curve is closer to the in-vivo absorption trend.
Further, the extraction rate of the dissolution liquid and the supplement rate of the dissolution medium are 5 mL/min, 6 mL/min, 8 mL/min, 10 mL/min or 12 mL/min.
Furthermore, the rotating speed of the rotating basket is 50-100 rpm. Preferably, the rotational speed of the spin basket is 100 rpm. Under the condition of the rotating speed, the dissolution rate is high, and hydrodynamic disturbance can not occur.
Further, the fixed time points are 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240min and the like until the dissolution of the felodipine sustained-release tablets is completed. The felodipine sustained-release tablets are completely dissolved out in 240min, no residue is left in a rotating basket, and the dissolution quality controllability and the dissolution stability of the sustained-release tablets are greatly improved.
Further, the two-chamber model experimental device for simulating the dissolution and transmembrane absorption process of the insoluble oral drug preparation in vivo is disclosed in patent CN 201920858418.4.
Further, the specification of the felodipine sustained-release tablet is 5 mg.
Compared with the prior art, the invention has the following beneficial effects:
the invention adopts a two-chamber model experimental device for simulating the in-vivo dissolution and transmembrane absorption processes of the insoluble oral pharmaceutical preparation, realizes the maintenance of the constant temperature of a dissolution medium, and ensures the simulation of the physiological temperature of the in-vivo gastrointestinal tract. Compared with the release mode of a common flow cell dissolution instrument and the existing pulp plate method, the invention adopts transverse shearing force for stirring, can overcome the cohesive force of the medicine and destroy the hydrogel structure formed on the surface of the medicine, can simulate the physiological peristalsis and food friction of the gastrointestinal tract in vivo, and has promotion effect on the dissolution/release process of the medicine; the filter membrane is adopted to filter undissolved drugs, the in vivo absorption effect of the drugs can be simulated, the simulation of the in vitro dissolution and in vivo absorption of the drugs is closer to the process of the absorption of human bodies to the drugs, and the judgment of the correlation of the in vitro dissolution and in vivo absorption is facilitated.
The method of the invention keeps the leakage groove condition of the felodipine sustained-release tablet medicament preparation by continuously inputting the fresh medium and outputting the medicament-containing medium, and effectively simulates the in vivo absorption state by forming an open dissolution model. The dissolution capacity of the felodipine sustained-release tablet in unit time is distinguished by detecting the drug concentration of different sampling points, so that the absorption capacity of the felodipine sustained-release tablet in a human body is predicted.
The embodiment of the invention proves that the method simulates the in-vivo absorption process, ensures the accuracy of in-vitro dissolution experiments, realizes that the dissolution curve trend measured by the in-vitro dissolution experiments is consistent with the in-vivo drug absorption-time curve trend of BE experiments, can evaluate the advantages and disadvantages of felodipine sustained-release tablets so as to guide the research and development of preparations, also makes a prediction on bioequivalence, improves the success rate of bioequivalence experiments, and ensures the biological effectiveness of the drugs after being marketed.
In comparative example 1 and example 3, the dissolution curves of the reference formulations are similar (both the line shape and the trend are the same), further illustrating that the method provided by the present invention has good reproducibility and good stability of the dissolution method.
In comparative example 1 and example 3, the dissolution curves and dissolution rates of the test preparations are different, and the test preparations and the reference preparations have better discrimination, so that the quality and the process difference between the reference preparations and the test preparations can be effectively distinguished, and the similarity and the quality consistency of the reference preparations can be evaluated.
Comparing example 1 and example 3, with the experimental data of example 2, the in vitro dissolution curve and in vivo BE experimental trend are consistent, and the prediction is made for bioequivalence, so that the success rate of bioequivalence experiment can BE improved, the bioavailability of the drug on the market can BE ensured, and the research and development risk can BE reduced.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings without creative efforts.
Figure 1 mean differential dissolution profile of a reference formulation of 5 mg felodipine sustained release tablets in example 1.
Figure 2 mean cumulative dissolution profile of a reference formulation of 5 mg felodipine sustained release tablets of example 1.
Figure 3 mean differential dissolution profiles of the reference and test formulations of the 5 mg sustained release felodipine tablet of example 3.
Figure 4 mean cumulative dissolution profiles of the reference and test formulations of the 5 mg sustained release felodipine tablet of example 3.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. These examples are intended to illustrate the invention and are not intended to limit the scope of the invention.
Example 1
A method for determining in-vitro dissolution of felodipine sustained-release tablets is to dissolve the felodipine sustained-release tablets by using a two-chamber model experimental device for simulating in-vivo dissolution and transmembrane absorption processes of insoluble oral pharmaceutical preparations, and comprises the following specific steps:
1) dissolving media enter the porous filter membrane cup through the action of the liquid inlet pump, when the volumes of the dissolving media in the porous filter membrane cup and the dissolving cup in the outer chamber are the same, the liquid outlet pump is started, the working frequencies of the liquid inlet pump and the liquid outlet pump are consistent, and the total volume of the dissolving media is kept unchanged; the dissolution medium is 0.3% sodium dodecyl sulfate pH 6.8 phosphate buffer solution, and the aperture of the filter membrane coated outside the porous filter membrane cup is 0.45 μm;
2) placing the felodipine sustained-release tablets in a rotating basket, wherein the rotating speed of the rotating basket is 100 rpm, filtering the dissolution liquid by a filter membrane, continuously extracting the dissolution liquid, wherein the extraction speed of the dissolution liquid and the supplement speed of a dissolution medium are both 6 mL/min, and measuring the concentration of felodipine in the dissolution liquid at time points of 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 210 and 240min until the felodipine sustained-release tablets are completely dissolved;
3) determining the average dissolution concentration of felodipine at different time points in a dissolution liquid by adopting a high-performance liquid phase, obtaining an average differential dissolution curve graph between the average dissolution concentration and the dissolution time of felodipine by corresponding time points and the average dissolution concentration of felodipine, and obtaining an accumulated dissolution curve graph between accumulated dissolution mass fraction and dissolution time according to a differential dissolution relation;
the concentration of felodipine in the dissolution liquid is determined by adopting a high performance liquid phase, and the specific process is as follows: after the dissolution liquid is subjected to centrifugal treatment, precisely measuring 20 mu L of the dissolution liquid, injecting the solution into a high performance liquid chromatograph, recording a chromatogram, and calculating the concentration of the corresponding felodipine; the centrifugal treatment conditions are as follows: rotor No. 2, 4000rpm, 5 min.
Chromatographic conditions of the high performance liquid chromatography: c18 (20-H046); mobile phase: methanol-acetonitrile-ultrapure water = volume ratio (5: 3: 2); flow rate: 1 mL/min; wavelength: 238 nm; sample introduction amount: 20 mu L of the solution; column temperature: 35 ℃ is carried out.
Reference formulation: felodipine sustained-release tablets with specification of 5 mg;
preparation one to be tested: felodipine sustained-release tablets with specification of 5 mg;
under the dissolution conditions, in-vitro dissolution results of a reference felodipine sustained-release tablet and two tested preparations are shown in fig. 1-2, the cumulative dissolution rate of the first tested preparation is slightly lower than that of the reference preparation, and the differential dissolution rate of the first tested preparation is also slightly lower than that of the reference preparation 30min after the start of dissolution.
Example 2
The pre-meal bioequivalence study is carried out on 12 healthy volunteers by adopting random, open, three-cycle and cross experimental design, the washout period among cycles is 7 days, 5 mg/time of felodipine sustained-release tablet reference preparation or test preparation is respectively orally taken by the volunteers every week, 1 time is daily, and the blood sampling time is designed to be 4 mL of upper limb venous blood collected respectively before administration (0 h) and 10min, 20min, 30min, 45min, 1.0h, 1.25h, 1.5h, 1.75h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 15h, 24h and 36h after administration. The samples were centrifuged (3,500 rpm, 10 min), and plasma was separated and stored in an ultra-low temperature freezer at-80 ℃. Specifically, 100 μ L of plasma sample is taken, 600 μ L of anhydrous methanol (containing internal standard) is added, vortexed for 5min, fully and uniformly mixed, centrifuged at 12,000 rpm for 10min, and the supernatant is taken to enter an HPLC-MS (high performance liquid chromatography-tandem mass spectrometer) for analyzing the content of felodipine in plasma.
The conclusion is shown in table 1:
TABLE 1 summary of major pharmacokinetic parameters for fasting felodipine
TABLE 2 fasting felodipine LnCmaxAnd LnAUC double unilateral t-test and 90% confidence interval
The results of the in vivo BE preliminary experiments show that T of the tested preparation ImaxSlightly slower than the reference formulation, while the AUC for the test formulation one was slightly lower than the reference formulation. The in vitro dissolution test result is consistent with the in vivo BE preliminary test trend.
Example 3
A method for determining in-vitro dissolution of felodipine sustained-release tablets is to dissolve the felodipine sustained-release tablets by using a two-chamber model experimental device for simulating in-vivo dissolution and transmembrane absorption processes of insoluble oral pharmaceutical preparations, and comprises the following specific steps:
1) dissolving media enter the porous filter membrane cup through the action of the liquid inlet pump, when the volumes of the dissolving media in the porous filter membrane cup and the dissolving cup in the outer chamber are the same, the liquid outlet pump is started, the working frequencies of the liquid inlet pump and the liquid outlet pump are consistent, and the total volume of the dissolving media is kept unchanged; the dissolution medium is 0.3% sodium dodecyl sulfate pH 6.8 phosphate buffer solution, and the aperture of the filter membrane coated outside the porous filter membrane cup is 0.45 μm;
2) placing the felodipine sustained-release tablets in a rotating basket, wherein the rotating speed of the rotating basket is 100 rpm, filtering the dissolution liquid by a filter membrane, continuously extracting the dissolution liquid, wherein the extraction speed of the dissolution liquid and the supplement speed of a dissolution medium are both 6 mL/min, and measuring the concentration of felodipine in the dissolution liquid at a fixed time point until the felodipine sustained-release tablets are completely dissolved;
3) determining the average dissolution concentration of felodipine at different time points in a dissolution liquid by adopting a high-performance liquid phase, obtaining an average differential dissolution curve graph between the average dissolution concentration and the dissolution time of felodipine by corresponding time points and the average dissolution concentration of felodipine, and obtaining an accumulated dissolution curve graph between accumulated dissolution mass fraction and dissolution time according to a differential dissolution relation;
the concentration of felodipine in the dissolution liquid is determined by adopting a high performance liquid phase, and the specific process is as follows: the concentration of felodipine in the dissolution liquid is determined by adopting a high performance liquid phase, and the specific process is as follows: after the dissolution liquid is subjected to centrifugal treatment, precisely measuring 20 mu L of the dissolution liquid, injecting the solution into a high performance liquid chromatograph, recording a chromatogram, and calculating the concentration of the corresponding felodipine; the centrifugal treatment conditions are as follows: rotor No. 2, 4000rpm, 5 min.
Chromatographic conditions of the high performance liquid chromatography: c18 (20-H046); mobile phase: methanol-acetonitrile-ultrapure water = volume ratio (5: 3: 2); flow rate: 1 mL/min; wavelength: 238 nm; sample introduction amount: 20 mu L of the solution; column temperature: 35 ℃ is carried out.
Reference formulation: felodipine sustained-release tablets with specification of 5 mg;
test formulation two: felodipine sustained-release tablets with specification of 5 mg;
test formulation three: felodipine sustained-release tablets with specification of 5 mg;
test formulation four: felodipine sustained-release tablets with specification of 5 mg;
under the dissolution conditions, in-vitro dissolution results of a reference felodipine sustained-release tablet and two tested preparations are shown in figures 3-4, and experimental results show that the cumulative dissolution rates of the three tested preparations are slightly higher than that of the reference preparation, and the cumulative dissolution rates of the second tested preparation and the reference preparation are closer. As can be seen from the differential dissolution curves, the differential dissolution curves of the second test preparation and the reference preparation are relatively close, and the dissolution behaviors of the two preparations are similar. In addition, the dissolution rates of the test formulation three and the test formulation four were slightly faster than the reference formulation.
In the present example, the formulations of the second to fourth test preparations were subjected to fine adjustment of the component ratio based on the first test preparation in examples 1 to 2. Through the experiment of the embodiment 3 of the invention, the dissolution rates of the obtained second to fourth test preparations are higher than that of the first test preparation. Based on the experimental conclusions of examples 1-2 regarding the first test preparation, the dissolution behavior of the second test preparation is most similar to that of the reference preparation, and further BE preliminary experiments of the second test preparation can BE considered subsequently.
Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (9)
1. A method for determining in-vitro dissolution of felodipine sustained-release tablets is characterized in that the felodipine sustained-release tablets are dissolved by using a two-chamber model experimental device for simulating the in-vivo dissolution and transmembrane absorption processes of insoluble oral pharmaceutical preparations, and the method comprises the following specific steps:
1) dissolving media enter the porous filter membrane cup through the action of the liquid inlet pump, when the volumes of the dissolving media in the porous filter membrane cup and the dissolving cup in the outer chamber are the same, the liquid outlet pump is started, the working frequencies of the liquid inlet pump and the liquid outlet pump are consistent, and the total volume of the dissolving media is kept unchanged; the dissolution medium is 0.1-0.5% lauryl sodium sulfate phosphate buffer solution with the pH value of 6.8, and the aperture of the filter membrane coated outside the porous filter membrane cup is 0.45 mu m;
2) placing the felodipine sustained-release tablets in a rotating basket, wherein the rotating speed of the rotating basket is 50-300 rpm, filtering the dissolution liquid by a filter membrane, continuously extracting the dissolution liquid, wherein the extraction speed of the dissolution liquid and the supplement speed of a dissolution medium are both 5-12 mL/min, and measuring the concentration of felodipine in the dissolution liquid at a fixed time point until the felodipine sustained-release tablets are completely dissolved;
3) and (3) measuring the average dissolution concentration of felodipine at different time points in the dissolution liquid by adopting a high-performance liquid phase, obtaining an average differential dissolution curve graph between the average dissolution concentration and the dissolution time of felodipine according to the corresponding time points and the average dissolution concentration of felodipine, and obtaining an accumulated dissolution curve graph between the accumulated dissolution mass fraction and the dissolution time according to the differential dissolution relation.
2. The method for determining in vitro dissolution of a felodipine sustained release tablet according to claim 1, wherein the dissolution medium is 0.1%, 0.15%, 0.2%, 0.3%, 0.5% sodium lauryl sulfate in phosphate buffer pH 6.8.
3. The method for determining in vitro dissolution of felodipine sustained-release tablets according to claim 1, wherein the 0.1-0.5% sodium dodecyl sulfate phosphate buffer solution with pH 6.8 is 1000 mL of phosphate buffer solution containing 1-5 g of sodium dodecyl sulfate.
4. The method for determining in-vitro dissolution of the felodipine sustained-release tablet according to claim 1, wherein the concentration of felodipine in the dissolution liquid is determined by adopting a high performance liquid chromatography, and the specific process comprises the following steps: after the dissolution liquid is subjected to centrifugal treatment, precisely measuring 20 mu L of the dissolution liquid, injecting the solution into a high performance liquid chromatograph, recording a chromatogram, and calculating the concentration of the corresponding felodipine; the centrifugal treatment conditions are as follows: rotor No. 2, 4000rpm, 5 min;
chromatographic conditions of the high performance liquid chromatography: a C18 column; mobile phase: the volume ratio of the methanol to the acetonitrile to the ultrapure water is 5:3: 2; flow rate: 1 mL/min; wavelength: 238 nm; sample introduction amount: 20 mu L of the solution; column temperature: 35 ℃ is carried out.
5. The method for determining in vitro dissolution of a felodipine sustained-release tablet according to claim 1, wherein the temperature of the dissolution medium is controlled to (37 ± 0.5) ° c.
6. The method for determining in vitro dissolution of felodipine sustained-release tablets according to claim 1, wherein the extraction rate of the dissolution fluid and the supplement rate of the dissolution medium are 5 mL/min, 6 mL/min, 8 mL/min, 10 mL/min or 12 mL/min.
7. The method for determining in vitro dissolution of felodipine sustained-release tablets according to claim 1, wherein the rotating basket rotates at 50-100 rpm.
8. The method for determining in vitro dissolution of a felodipine sustained-release tablet according to claim 1, wherein the fixed time points are 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240min until completion of dissolution of the felodipine sustained-release tablet.
9. The method for determining in vitro dissolution of a felodipine sustained-release tablet according to claim 1, wherein the felodipine sustained-release tablet has a specification of 5 mg.
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| CN113109467A (en) * | 2021-03-30 | 2021-07-13 | 湖南慧泽生物医药科技有限公司 | Method for determining in-vitro dissolution of nifedipine sustained-release tablets |
| CN114646709A (en) * | 2022-05-23 | 2022-06-21 | 湖南慧泽生物医药科技有限公司 | Method for determining in-vitro dissolution of atorvastatin calcium tablets and application |
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| CN114646709A (en) * | 2022-05-23 | 2022-06-21 | 湖南慧泽生物医药科技有限公司 | Method for determining in-vitro dissolution of atorvastatin calcium tablets and application |
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