CN114137130A - Method for detecting release degree of pramipexole dihydrochloride sustained-release tablets - Google Patents
Method for detecting release degree of pramipexole dihydrochloride sustained-release tablets Download PDFInfo
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Abstract
The invention provides a method for detecting the release rate of pramipexole dihydrochloride sustained-release tablets, which comprises the following steps: dissolving the pramipexole dihydrochloride sustained-release tablets in a dissolving medium containing hexadecyl trimethyl ammonium bromide, and measuring the release degree of the pramipexole dihydrochloride sustained-release tablets by adopting high performance liquid chromatography. The dissolution medium in the detection method can improve the drug release amount of the pramipexole dihydrochloride sustained-release tablets, and the purpose of analysis is achieved by developing proper chromatographic conditions.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a method for detecting the release rate of pramipexole dihydrochloride sustained-release tablets.
Background
The pramipexole dihydrochloride sustained-release tablet is a nerve medicament and can be used for treating idiopathic parkinsonism. Parkinson's disease is a degenerative disease of the central nervous system, and is mainly manifested by slow movements of the patient, tremors in the hands and feet or other parts of the body, and a decrease in the softness and coordination of the patient's body. Pramipexole dihydrochloride is a non-ergot dopamine receptor agonist and can stimulate dopamine receptors highly selectively so as to improve the symptoms of patients.
CN105456216A discloses a pramipexole dihydrochloride sustained-release tablet composition and a preparation method thereof, wherein the composition comprises the following components in percentage by weight: 0.1-1% of pramipexole dihydrochloride, 10-40% of hydroxypropyl methylcellulose, 25-50% of polyacrylic resin, 20-60% of pregelatinized starch, 0.3-1.5% of colloidal silicon dioxide and 0.5-1% of magnesium stearate. The pramipexole dihydrochloride sustained-release tablet composition takes hydrophilic gel skeleton hydroxypropyl methylcellulose and non-hydrophilic skeleton material polyacrylic resin as sustained-release skeletons, and the hydroxypropyl methylcellulose and the polyacrylic resin form intricate channels to retard diffusion of drug molecules, so that the release rate of the drug can be effectively reduced, and sustained release is realized.
CN104367562A discloses a pramipexole dihydrochloride sustained-release tablet and a preparation method thereof, wherein the pramipexole dihydrochloride sustained-release tablet comprises 0.1-1.5% of pramipexole dihydrochloride dihydrate, 40.0-75.0% of water-insoluble swelling framework material, 0.5-3.0% of glidant, 0.5-3.0% of lubricant and 20.0-58.9% of other medicinal carriers in percentage by weight. When a matrix tablet formed by a water-insoluble swelling matrix material in the pramipexole dihydrochloride sustained-release tablet is contacted with an aqueous medium, the matrix tablet can maintain strong matrix strength in vivo, is not easily influenced by food to cause dose burst release, and has a good sustained-release effect.
Pramipexole dihydrochloride sustained release preparations developed at present are various, but the pharmacopeia does not include a chapter for pramipexole dihydrochloride sustained release tablets, and a recommended method for the release degree of pramipexole dihydrochloride sustained release tablets is to use 500mL of 0.05M phosphate buffer solution with ph6.8 as an elution medium and measure the release degree by a basket method. Pramipexole dihydrochloride is a substance which is easy to dissolve in water, the solubility of the pramipexole dihydrochloride in a phosphate buffer solution with the pH value of 6.8 is 446mg/mL, and the condition of a leak groove is met, but some pramipexole dihydrochloride sustained-release preparations cannot meet the requirement of basic release under the condition, so that a novel method for detecting the release degree of the pramipexole dihydrochloride sustained-release tablets is developed, and the pramipexole dihydrochloride sustained-release tablets can completely release (the release degree is more than 85%) in the release degree experiment process, so that the important significance is realized.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide a method for detecting the release degree of a pramipexole dihydrochloride sustained-release tablet, wherein a dissolution medium in the detection method consists of water, buffer salt and hexadecyl trimethyl ammonium bromide, and the release degree of the pramipexole dihydrochloride sustained-release tablet is analyzed by adopting high performance liquid chromatography. The dissolution medium in the determination method can improve the release amount of the pramipexole dihydrochloride sustained-release tablets, and the analysis purpose is achieved by developing proper chromatographic conditions, the analysis time of the detection method is short, the anti-interference performance is strong, the sensitivity is high, and the detection method disclosed by the invention meets the requirements of Chinese pharmacopoeia and guiding principles in the aspects of system applicability, specificity, repeatability, precision, recovery rate, stability and the like.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides a method for detecting the release rate of pramipexole dihydrochloride sustained-release tablets, which comprises the following steps: dissolving the pramipexole dihydrochloride sustained-release tablets in a dissolving medium containing hexadecyl trimethyl ammonium bromide, and measuring the release degree of the pramipexole dihydrochloride sustained-release tablets by adopting high performance liquid chromatography.
The dissolution medium consists of water, buffer salt and hexadecyl trimethyl ammonium bromide, the surfactant can improve the wettability of the surface of hydrophobic drug particles, so that the release condition of the drug is improved, the surfactant is added into the dissolution medium, the surface tension of the medium is reduced, micelles are solubilized, and the release rate of the drug is increased. The invention improves the situation that the medicine is difficult to completely release due to the swelling of the high-viscosity hypromellose by adding the hexadecyl trimethyl ammonium bromide.
Preferably, cetyl trimethylammonium bromide and phosphate buffer are included in the dissolution medium.
Preferably, the mass ratio of the cetyl trimethyl ammonium bromide to the phosphate buffer is (0.005-0.015):100, and may be, for example, 0.005:100, 0.007:100, 0.009:100, 0.01:100, 0.011:100, 0.013:100, or 0.015: 100.
The cetyl trimethyl ammonium bromide is used as a surfactant, the addition amount of the cetyl trimethyl ammonium bromide influences the final release effect, the improvement effect on the release degree is lower due to the excessively low content of the surfactant, the release is too fast due to the excessively high content of the surfactant, and the dissolution method has no distinguishing force and influences the test of the release degree.
Preferably, the phosphate buffer comprises the following components in parts by weight: 0.67-0.69 part of monopotassium phosphate, 0.088-0.092 part of sodium hydroxide, 0.01-1 part of pH regulator and 98-100 parts of water.
In the present invention, the weight portion of the monopotassium phosphate is 0.67-0.69 portion, and may be, for example, 0.67 portion, 0.68 portion, 0.69 portion, or the like.
In the present invention, the weight portion of the sodium hydroxide is 0.088 to 0.092, and may be, for example, 0.088, 0.089, 0.09, 0.091, or 0.092.
The pH adjuster in the present invention may be used in an amount of 0.01 to 1 part by weight, for example, 0.01 part, 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part or 1 part.
The weight portion of the water in the invention is 98-100, such as 98, 98.2, 98.4, 98.6, 98.8, 99, 99.2, 99.4, 99.6, 99.8 or 100.
Preferably, the pH adjusting agent comprises sodium hydroxide and/or phosphoric acid.
Preferably, the pH of the phosphate buffer is 6.6-7.0, and may be, for example, 6.6, 6.65, 6.7, 6.75, 6.8, 6.85, 6.9, 6.95, 7.0, or the like.
Preferably, the specific operation of dissolution is: taking the pramipexole dihydrochloride sustained-release tablets, adopting a paddle method to dissolve the pramipexole dihydrochloride sustained-release tablets in a dissolving medium containing hexadecyl trimethyl ammonium bromide, and then sampling to obtain a test solution.
Preferably, the volume of the dissolution medium is 890-910mL, such as 890mL, 900mL, 910mL or the like, the dissolution temperature is 35-38 deg.C, such as 35 deg.C, 35.5 deg.C, 36 deg.C, 36.5 deg.C, 37 deg.C, 37.5 deg.C, 38 deg.C or the like, and the dissolution rotation speed is 75-100rpm, such as 75rpm or 100rpm or the like.
Preferably, the sample is taken after 1 to 24 hours of dissolution, and may be, for example, 1 hour, 2 hours, 4 hours, 6 hours, 9 hours, 12 hours, 16 hours, 20 hours, 24 hours, or the like.
Preferably, the test solution is further subjected to filtration and/or centrifugation.
Preferably, the pore size of the filtration is 0.22-0.45. mu.m, and may be, for example, 0.22. mu.m, 0.25. mu.m, or 0.45. mu.m.
Preferably, the filter membrane material used for filtration comprises a water-based filter membrane and/or a nylon filter membrane.
Preferably, the rotation speed of the centrifugation is 3000-5000rpm, such as 3000rpm, 3500rpm, 4000rpm, 4500rpm or 5000rpm, and the like, and the time of the centrifugation is 5-10min, such as 5min, 6min, 7min, 8min, 9min or 10min, and the like.
Preferably, the chromatographic column of the high performance liquid chromatography takes octadecylsilane chemically bonded silica as a filler.
Preferably, the size of the column for high performance liquid chromatography is (100-.
Preferably, the mobile phase of the high performance liquid chromatography comprises phosphate buffer containing octane sulfonate and acetonitrile.
Preferably, the volume ratio of the phosphate buffer containing octane sulfonate to acetonitrile is (71-75): 25-29, and can be, for example, 71:29, 72:28, 73:27, 74:26 or 75: 25.
In the invention, the ratio of the organic phase to the phosphate buffer solution in the mobile phase can improve the peak appearance of the chromatogram, maintain reasonable separation degree, improve the peak shape of the chromatographic peak, shorten the peak appearance time and improve the analysis efficiency. The proportion of the organic phase is increased, the peak emergence speed of the pramipexole dihydrochloride is increased, but the main peak is changed into two peaks at the same time, so that the requirement on the applicability of the system cannot be met; the proportion of an organic phase is reduced, the peak emergence speed of the pramipexole dihydrochloride is slowed, the detection efficiency is influenced, and the requirement on the applicability of the system cannot be met.
Preferably, the octane sulfonate is sodium octane sulfonate.
In the invention, the sodium octane sulfonate is an ion pair reagent, and the retention time of the pramipexole dihydrochloride main peak can be maintained by adding the sodium octane sulfonate, so that the drift of the retention time of the main peak is reduced.
Preferably, the octane sulfonate is added in an amount of 0.49 to 0.51% by mass, for example, 0.49%, 0.50%, or 0.51% by mass based on the total mass of the phosphate buffer.
In the invention, the addition amount of the octane sulfonate is too low or too high, which is not beneficial to the analysis process of the high performance liquid chromatography, and the addition amount is too low, which cannot play a role in stabilizing the retention time, and the addition amount is too high, which can affect the pressure and peak shape of the chromatographic column.
Preferably, the pH of the octane sulfonate containing phosphate buffer is 2.8-3.2, and may be, for example, 2.8, 2.85, 2.9, 2.95, 3.0, 3.05, 3.1, 3.15, 3.2, or the like.
Preferably, the phosphate buffer comprises the following components in parts by weight: 0.89-0.93 part of monopotassium phosphate, 0.02-0.15 part of phosphoric acid and 98-100 parts of water.
In the present invention, the weight part of the potassium dihydrogen phosphate in the phosphate buffer solution in the mobile phase is 0.89 to 0.93 parts, and may be, for example, 0.89 part, 0.90 part, 0.91 part, 0.92 part, 0.93 part, or the like.
In the present invention, the phosphate buffer in the mobile phase may contain 0.02 to 0.15 parts by weight of phosphoric acid, for example, 0.02 parts, 0.04 parts, 0.06 parts, 0.08 parts, 0.1 parts, 0.12 parts, or 0.15 parts.
In the present invention, the phosphate buffer in the mobile phase contains 98 to 100 parts by weight of water, and may be, for example, 98 parts, 98.2 parts, 98.4 parts, 98.6 parts, 98.8 parts, 99 parts, 99.2 parts, 99.4 parts, 99.6 parts, 99.8 parts, or 100 parts.
Preferably, the flow rate of the high performance liquid chromatography is 1.4-1.6mL/min, and may be, for example, 1.4mL/min, 1.5mL/min, or 1.6mL/min, etc.
In the invention, the flow velocity of the mobile phase is too low, the peak-off time of the main peak of the pramipexole dihydrochloride can be prolonged, and the requirement on the applicability of the system can not be met; the flow rate is too high, the main peak and the interference peak of the pramipexole dihydrochloride are difficult to separate, and the separation degree cannot meet the requirement.
Preferably, the analysis time of the high performance liquid chromatography is 4-6min, for example, 4min, 4.5min, 5min, 5.5min or 6 min.
Preferably, the high performance liquid chromatography column temperature is 38-42 ℃, for example, can be 38 ℃, 39 ℃, 40 ℃, 41 ℃ or 42 ℃.
In the present invention, column temperature can affect the pressure in the analysis system, temperature drop can increase pressure, affect the stability of the analysis, and column temperature over-high can reduce the useful life of the column.
Preferably, the detection wavelength of the high performance liquid chromatography is 260-264nm, and can be 260nm, 261nm, 262nm, 263nm, 264nm and the like.
Preferably, the sample injection volume of the high performance liquid chromatography is 98-102 μ L, such as 98 μ L, 99 μ L, 100 μ L, 101 μ L or 102 μ L.
As a preferred embodiment of the present invention, the detection method comprises the steps of:
(1) dissolution of the sample: taking the pramipexole dihydrochloride sustained-release tablets, adopting a paddle method to dissolve in a dissolution medium containing hexadecyl trimethyl ammonium bromide, then sampling, filtering and/or centrifuging, and sampling at dissolution time points of 1h, 2h, 4h, 6h, 9h, 12h, 16h, 20h and 24h respectively to obtain test solution at different time points;
wherein the mass ratio of the cetyl trimethyl ammonium bromide to the phosphate buffer solution is (0.005-0.015): 100; the volume of the dissolution medium is 890-910mL, the dissolution temperature is 35-38 ℃, and the dissolution rotation speed is 75-100 rpm;
(2) and (3) detection of the sample: detecting the test solution at different time points by adopting high performance liquid chromatography, and calculating to obtain the release degree;
the chromatographic column of the high performance liquid chromatography takes octadecylsilane chemically bonded silica as a filler, and the specification of the chromatographic column of the high performance liquid chromatography is (100) and 150mm multiplied by (3-4.6mm) and 4-5 mu m; the mobile phase comprises phosphate buffer solution containing octane sulfonate and acetonitrile in a volume ratio of (71-75) to (25-29); the flow rate of the high performance liquid chromatography is 1.4-1.6mL/min, the analysis time is 4-6min, the column temperature is 38-42 ℃, the detection wavelength is 260-264nm, and the sample injection volume is 98-102 mu L.
In the method for detecting the release rate of the pramipexole dihydrochloride sustained-release tablets, the calculation formula of the release rate is as follows:
degree of release (%) ═ aSample (A)×WTo pair×PTo pair×VSample (A))/(ATo pair×VTo pairX specification) x 100%
Wherein:
Asample (A): peak area of pramipexole peak of the test solution;
Ato pair: peak area of pramipexole peak of the control solution;
Wto pair: weighing pramipexole dihydrochloride reference substances (mg);
Pto pair: content (%) of pramipexole dihydrochloride reference substance;
Vsample (A): dissolution medium volume (mL);
Vto pair: pramipexole dihydrochloride reference substance dilution times.
The recitation of numerical ranges herein includes not only the above-recited numerical values, but also any numerical values between non-recited numerical ranges, and is not intended to be exhaustive or to limit the invention to the precise numerical values encompassed within the range for brevity and clarity.
The system refers to an equipment system, or a production equipment.
Compared with the prior art, the invention has the beneficial effects that:
(1) the condition that the medicine is difficult to completely release due to high-viscosity hypromellose swelling can be improved by adding the cetyl trimethyl ammonium bromide.
(2) The proportion of the organic phase and the buffer salt solution in the mobile phase can improve the peak appearance of the chromatogram, maintain reasonable separation degree, improve the peak shape of the chromatographic peak, shorten the peak appearance time and improve the analysis efficiency.
(3) The detection method disclosed by the invention is short in time consumption and high in analysis speed, and can reduce the degradation of the medicine in the analysis process; the used reagent has low cost, and the analysis cost can be reduced; the detection method provided by the invention meets the requirements of Chinese pharmacopoeia and guiding principles in the aspects of system applicability, specificity, repeatability, precision, recovery rate, stability and the like.
(4) The method of the detection method of the invention verifies that the data is as follows:
the method for detecting the release rate of the pramipexole dihydrochloride sustained release tablets provided by the invention enables the pramipexole dihydrochloride sustained release tablets to achieve complete release (the release rate is more than 85%) in the release rate experiment process, and meets the requirements of Chinese pharmacopoeia and guiding principles in the aspects of system applicability, specificity, repeatability (precision), recovery rate, stability and the like.
The methodology in the preferred embodiment is examined as follows:
the retention time of the pramipexole dihydrochloride is 2.7-3.7min, the retention time of the blank solution is not interfered, and the applicability of the system meets the requirement.
The recovery rate at 50% concentration (low concentration) was 99%, the recovery rate at 100% concentration (medium concentration) was 99-101%, and the recovery rate at 150% concentration (high concentration) was 98-100%, all of which were in the range of 97.0-103.0%, and were satisfactory.
Taking the reference solution and continuously feeding into 6 needles, wherein the% RSD of the peak area of the obtained pramipexole dihydrochloride chromatographic peak is 0.2-0.3, and the% RSD is less than 3.0, which indicates that the precision of the detection method is good.
The reference solution and the test solution are placed under an experiment table at room temperature for three days, the content of the pramipexole dihydrochloride serving as the main component is 99-101% of the labeled amount, and the pramipexole dihydrochloride is stable within three days, which indicates that the detection method meets the requirements.
Drawings
FIG. 1 is a chromatogram of the dissolution medium of example 1.
FIG. 2 is a chromatogram of the control solution of example 1.
FIG. 3 is a chromatogram of a 24h sample solution in example 1.
FIG. 4 is a chromatogram of a 24h sample solution in example 13.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
The examples do not show the specific techniques or conditions, according to the technical or conditions described in the literature in the field, or according to the product specifications. The reagents or apparatus used are conventional products commercially available from normal sources, not indicated by the manufacturer.
Before the release rate of the pramipexole dihydrochloride sustained-release tablets is detected, the methodology investigation of a high performance liquid chromatography method is required, and comprises the following steps:
(1) sample introduction reproducibility: taking the reference substance solution and continuously feeding into 6 needles, and calculating the% RSD of the peak area of the main peak of the pramipexole dihydrochloride chromatogram.
(2) The specificity is as follows: taking blank solution and blank adjuvant, and adding into 1 needle.
(3) And (3) recovery rate: recovery was examined at three concentration levels.
(4) Repeatability: sampling the sample solution in each dissolution cup at each sampling point; and taking the last sampling point of one cup, repeatedly sampling for 6 times, and injecting sample solution for 6 times.
(5) Stability: the reference solution and the sample solution were placed on a bench at 20-25 deg.C for three days, and the content of the main components was measured.
Preparing a reference substance solution: taking 10mg of pramipexole dihydrochloride reference substance, precisely weighing, placing in a 100mL measuring flask, dissolving with methanol and diluting to a scale mark. 2mL of the above solution was precisely measured and placed in a 200mL measuring flask, and diluted to the scale with a dissolution medium.
Solution formulation for accuracy (recovery) test: weighing 230mg of pramipexole dihydrochloride blank auxiliary materials, placing the blank auxiliary materials into a dissolution cup filled with 895mL of dissolution media, precisely measuring 5mL of pramipexole dihydrochloride solutions with a series of concentrations (the concentrations comprise 0.0075mg/mL, 0.075mg/mL and 0.3mg/mL) respectively, placing the solutions into the dissolution cup, and operating according to dissolution conditions.
In the method for detecting the release rate of the pramipexole dihydrochloride sustained-release tablets, the calculation formula of the release rate is as follows:
degree of release (%) ═ aSample (A)×WTo pair×PTo pair×VSample (A))/(ATo pair×VTo pairX specification) x 100%
Wherein:
Asample (A): peak area of pramipexole peak of the test solution;
Ato pair: peak area of pramipexole peak of the control solution;
Wto pair: weighing pramipexole dihydrochloride reference substances (mg);
Pto pair: content (%) of pramipexole dihydrochloride reference substance;
Vsample (A): dissolution medium volume (mL);
Vto pair: pramipexole dihydrochloride reference substance dilution times.
Example 1
The present embodiment provides a method for detecting the release rate of a pramipexole dihydrochloride sustained-release tablet, where the specifications of the pramipexole dihydrochloride sustained-release tablet in the present embodiment are as follows: 0.375mg, batch number: 19445001, containing 50% hypromellose K15M.
The detection method comprises the following steps:
(1) dissolution test
The dissolution medium was 0.01% cetyl trimethylammonium bromide in phosphate buffer ph 6.8:
dissolving 27.22g of monopotassium phosphate and 3.6g of sodium hydroxide in 4L of water, mixing, and adjusting the pH to 6.8 by using the sodium hydroxide; 0.4g of cetyltrimethylammonium bromide was added and mixed.
Dissolution conditions: using an Agilent dissolution instrument, adopting a United states Pharmacopeia <711> second method and adopting a paddle method, wherein the volume of a dissolution medium is 900mL, the rotating speed is set to be 100rpm, and the temperature is set to be: 37 ℃ is carried out.
And (3) dissolution operation: taking 6 pramipexole dihydrochloride sustained-release tablets, respectively putting into each dissolution cup, adopting a paddle method to dissolve in a dissolution medium containing hexadecyl trimethyl ammonium bromide, then sampling, taking 10mL of sample solution from each dissolution cup after the sampling time is 1h, 2h, 4h, 6h, 9h, 12h, 16h, 20h and 24h after the tablet feeding is started, filtering the sample solution by a 0.45 mu m needle filter head (manufacturer: Xinya, diameter: 25mm), discarding 3mL of primary filtrate, and taking a subsequent filtrate for detection.
(2) Detecting by high performance liquid chromatography
The mobile phase is a mixed solution of phosphate buffer solution with 0.5 percent of octane sodium sulfonate and pH3.0 and acetonitrile:
dissolving 9.1g of monopotassium phosphate and 5g of sodium octane sulfonate in 1L of water, mixing, and adjusting the pH to 3.0 by using phosphoric acid; the volume ratio of the phosphate buffer solution to the acetonitrile is 73: 27.
Chromatographic conditions are as follows:
the chromatographic column is a Watt-octadecyl silane bonded silica gel chromatographic column (Sunfire C18);
the column length is 150mm, the inner diameter is 4.6mm, and the particle size of the filling particles is 5 mu m; column temperature: 40 ℃;
flow rate: 1.5mL/min, detection wavelength: 264 nm;
sample introduction volume: 100 μ L, run time: and 5 min.
After balancing the instrument, sampling the filtered sample solution, the dissolution medium, the recovery rate test solution and the reference solution respectively.
Example 2
The present embodiment provides a method for detecting the release rate of a pramipexole dihydrochloride sustained-release tablet, where the specifications of the pramipexole dihydrochloride sustained-release tablet in the present embodiment are as follows: 0.375mg, batch number: 19445001, containing 50% hypromellose K15M.
The detection method comprises the following steps:
(1) dissolution test
The dissolution medium was 0.015% hexadecyltrimethylammonium bromide in ph7.0 phosphate buffer:
dissolving 27.6g of monopotassium phosphate and 3.68g of sodium hydroxide in 4L of water, mixing, and adjusting the pH to 7.0 by using the sodium hydroxide; 0.6g of cetyltrimethylammonium bromide was added and mixed.
Dissolution conditions: using an Agilent dissolution instrument, adopting a United states Pharmacopeia <711> second method and adopting a paddle method, wherein the volume of a dissolution medium is 900mL, the rotating speed is set to be 100rpm, and the temperature is set to be: 37 ℃ is carried out.
And (3) dissolution operation: taking 6 pramipexole dihydrochloride sustained-release tablets, respectively putting the 6 pramipexole dihydrochloride sustained-release tablets into each dissolution cup, sampling after dissolving in a dissolution medium containing hexadecyl trimethyl ammonium bromide by adopting a paddle method, taking 10mL of sample solution from each dissolution cup after 1h, 2h, 4h, 6h, 9h, 12h, 16h, 20h and 24h after the start of tablet feeding, centrifuging the sample solution at 5000rpm for 10min, and taking supernatant.
(2) Detecting by high performance liquid chromatography
The mobile phase is a mixed solution of phosphate buffer solution with 0.51 percent of sodium octane sulfonate and pH3.2 and acetonitrile:
dissolving 9.3g of monopotassium phosphate and 5.1g of sodium octane sulfonate in 1L of water, mixing, and adjusting the pH to 3.2 by using phosphoric acid; the volume ratio of the phosphate buffer solution to the acetonitrile is 74: 26.
Chromatographic conditions are as follows:
the chromatographic column is a Watt-octadecyl silane bonded silica gel chromatographic column (Sunfire C18);
the column length is 150mm, the inner diameter is 4.6mm, and the particle size of the filling particles is 5 mu m; column temperature: 40 ℃;
flow rate: 1.5mL/min, detection wavelength: 264 nm;
sample introduction volume: 100 μ L, run time: and 5 min.
After balancing the instrument, sampling the filtered sample solution, the dissolution medium, the recovery rate test solution and the reference solution respectively.
Example 3
The present embodiment provides a method for detecting the release rate of a pramipexole dihydrochloride sustained-release tablet, where the specifications of the pramipexole dihydrochloride sustained-release tablet in the present embodiment are as follows: 0.375mg, batch number: 19445001, containing 50% hypromellose K15M.
The detection method comprises the following steps:
(1) dissolution test
The dissolution medium was 0.005% cetyl trimethylammonium bromide in ph6.6 phosphate buffer:
dissolving 26.8g of potassium dihydrogen phosphate and 3.52g of sodium hydroxide in 4L of water, mixing, and adjusting the pH to 6.6 with sodium hydroxide; 0.2g of cetyltrimethylammonium bromide was added and mixed.
Dissolution conditions: using an Agilent dissolution instrument, adopting a United states Pharmacopeia <711> second method and adopting a paddle method, wherein the volume of a dissolution medium is 900mL, the rotating speed is set to be 100rpm, and the temperature is set to be: 37 ℃ is carried out.
And (3) dissolution operation: taking 6 pramipexole dihydrochloride sustained-release tablets, respectively putting into each dissolution cup, adopting a paddle method to dissolve in a dissolution medium containing hexadecyl trimethyl ammonium bromide, then sampling, taking 10mL of sample solution from each dissolution cup after the sampling time is 1h, 2h, 4h, 6h, 9h, 12h, 16h, 20h and 24h after the tablet feeding is started, filtering the sample solution by a 0.45 mu m needle filter head (manufacturer: Xinya, diameter: 25mm), discarding 3mL of primary filtrate, and taking a subsequent filtrate for detection.
(2) Detecting by high performance liquid chromatography
The mobile phase is phosphate buffer containing 0.49% sodium octane sulfonate and having pH 2.8:
dissolving 8.9g of monopotassium phosphate and 4.9g of sodium octane sulfonate in 1L of water, mixing, and adjusting the pH to 2.8 by using phosphoric acid; the volume ratio of the phosphate buffer solution to the acetonitrile is 72: 28.
Chromatographic conditions are as follows:
the chromatographic column is a Watt-octadecyl silane bonded silica gel chromatographic column (Sunfire C18);
the column length is 150mm, the inner diameter is 4.6mm, and the particle size of the filling particles is 5 mu m; column temperature: 40 ℃;
flow rate: 1.5mL/min, detection wavelength: 264 nm;
sample introduction volume: 100 μ L, run time: and 5 min.
After balancing the instrument, sampling the sample solution, the dissolution medium, the solution for recovery rate test and the reference substance solution filtered in the step (1) respectively.
Example 4
This example provides a method for measuring the release rate of pramipexole dihydrochloride sustained release tablets, which differs from example 1 only in that the dissolution medium is a phosphate buffer solution of ph6.8 containing 0.001% cetyltrimethylammonium bromide, and the rest of the parameters refer to example 1.
Example 5
This example provides a method for measuring the release rate of pramipexole dihydrochloride sustained release tablets, which differs from example 1 only in that the dissolution medium is a phosphate buffer solution with ph6.8 containing 0.02% cetyltrimethylammonium bromide, and the rest parameters refer to example 1.
Example 6
This example provides a method for detecting the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that the addition amount of sodium octane sulfonate in the mobile phase accounts for 0.25% of the total mass of the phosphate buffer solution, and the rest parameters refer to example 1.
Example 7
This example provides a method for detecting the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that the addition amount of sodium octane sulfonate in the mobile phase accounts for 0.75% of the total mass of the phosphate buffer solution, and the rest parameters refer to example 1.
Example 8
This example provides a method for detecting the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that the flow rate of the high performance liquid chromatography is 1mL/min, and the rest of parameters refer to example 1.
Example 9
This example provides a method for measuring the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that the flow rate of the high performance liquid chromatography is 1.8mL/min, and the rest of the parameters refer to example 1.
Example 10
This example provides a method for measuring the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that the volume ratio of the phosphate buffer solution containing octane sulfonate to acetonitrile in the mobile phase is 68:32, and the rest of the parameters refer to example 1.
Example 11
This example provides a method for measuring the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that the volume ratio of the phosphate buffer solution containing octane sulfonate to acetonitrile in the mobile phase is 78:22, and the rest of the parameters refer to example 1.
Example 12
This example provides a method for detecting the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that sodium octane sulfonate is not contained in the mobile phase, and the rest parameters refer to example 1.
Example 13
This example provides a method for detecting the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that the pramipexole dihydrochloride sustained release tablets have a specification of 0.75mg, and the lot number: 20473001 containing 50% hydroxypropylcellulose K15M, the rest of the parameters being as in example 1.
Comparative example 1
This example provides a method for measuring the release rate of pramipexole dihydrochloride sustained release tablets, which differs from example 1 only in that the dissolution medium does not contain cetyltrimethylammonium bromide, and the rest of the parameters refer to example 1.
Comparative example 2
This example provides a method for detecting the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that the cetyl trimethyl ammonium bromide in the dissolution medium is replaced by tween-80, and the rest parameters refer to example 1.
Comparative example 3
This example provides a method for detecting the release rate of pramipexole dihydrochloride sustained release tablets, which is different from example 1 only in that cetyl trimethyl ammonium bromide in the dissolution medium is replaced by sodium dodecyl sulfate, and the rest parameters refer to example 1.
Comparative example 4
This example provides a method for measuring the release of pramipexole dihydrochloride sustained release tablets, which differs from example 1 only in that hexadecyltrimethylammonium bromide in the dissolution medium is replaced by disodium lauryl sulfosuccinate monoester, and the remaining parameters refer to example 1.
The results of the methodological investigation in examples 1 to 13 and comparative examples 1 to 4 are shown in Table 1:
TABLE 1
Methodological observations of examples 1-3:
the retention time of the pramipexole dihydrochloride is 2.7-3.7min, the retention time of the blank solution is not interfered, and the applicability of the system meets the requirement.
The recovery rate at 50% concentration (low concentration) was 99%, the recovery rate at 100% concentration (medium concentration) was 99-101%, and the recovery rate at 150% concentration (high concentration) was 98-100%, all of which were in the range of 97.0-103.0%, and were satisfactory.
Taking the reference solution and continuously feeding into 6 needles, wherein the% RSD of the peak area of the obtained pramipexole dihydrochloride chromatographic peak is 0.2-0.3, and the% RSD is less than 3.0, which indicates that the precision of the detection method is good.
The reference solution and the test solution are placed under an experiment table at room temperature for three days, the content of the pramipexole dihydrochloride serving as the main component is 99-101% of the labeled amount, and the pramipexole dihydrochloride is stable within three days, which indicates that the detection method meets the requirements.
Fig. 1 is a chromatogram of the dissolution medium in example 1, and it can be seen from fig. 1 that the dissolution medium does not interfere with the main peak of the pramipexole dihydrochloride sustained-release tablet.
Fig. 2 is a chromatogram of the control solution in example 1, and it can be seen from fig. 2 that the separation between the main pramipexole dihydrochloride peak and the interfering peak meets the requirement of system applicability and the peak shape is good.
FIG. 3 is a chromatogram of a 24h sample solution in example 1.
FIG. 4 is a chromatogram of a 24h sample solution in example 13.
As can be seen from fig. 3 and 4, the detection method has good stability, stable retention time, normal peak shape and good separation degree from the interference peak.
The comparison of example 1, examples 6 to 7 and example 12 shows that too high or too low amount of sodium octane sulfonate in the mobile phase affects the appearance of the pramipexole dihydrochloride chromatogram peak. The octane sodium sulfonate is an ion pair reagent, the retention time of the pramipexole dihydrochloride main peak can be maintained by adding the octane sodium sulfonate, and the effect of stabilizing the retention time cannot be exerted if the addition amount is too low, in example 6, the addition amount of the octane sodium sulfonate is low, two chromatographic peaks appear, and the retention time is 1.8min and 2.4min respectively; in example 7, the addition amount of sodium octane sulfonate is too high, which affects the peak shape of pramipexole dihydrochloride and the pressure of an analysis system, and the retention time is prolonged to 4.1min, in example 12, the mobile phase does not contain sodium octane sulfonate, and the retention time of the main peak of pramipexole dihydrochloride is 1.0min, which does not meet the detection requirement.
The comparison between the example 1 and the examples 8 to 9 shows that the flow velocity of the mobile phase is too low, the peak emergence time of the pramipexole dihydrochloride is prolonged, the main peak retention time of the pramipexole dihydrochloride is 4.5min, and the requirement on the applicability of the system cannot be met; the flow rate is too high, the retention time of the main peak of the pramipexole dihydrochloride is 2.4min, the main peak of the pramipexole dihydrochloride cannot be separated from the interference peak, and the separation degree cannot meet the requirement.
The comparison between the example 1 and the examples 10 to 11 shows that two chromatographic peaks appear when the proportion of the organic phase is increased, the retention time is 1.6min and 1.8min respectively, the peak emergence speed of the pramipexole dihydrochloride is high, and the applicability requirement of the system cannot be met; the proportion of an organic phase is reduced, the peak emergence speed of the pramipexole dihydrochloride is reduced, the retention time is 8min, the retention time is too long, the detection efficiency is influenced, and the requirement on the applicability of the system cannot be met.
The results of the release measurements in examples 1-5, example 13 and comparative examples 1-4 are shown in Table 2:
TABLE 2
| Sample (I) | 1h | 2h | 4h | 6h | 9h | 12h | 16h | 20h | 24h |
| Example 1 | 18％ | 27％ | 41％ | 52％ | 64％ | 73％ | 81％ | 87％ | 90％ |
| Example 2 | 20％ | 29％ | 43％ | 54％ | 66％ | 75％ | 83％ | 89％ | 92％ |
| Example 3 | 13％ | 23％ | 36％ | 47％ | 59％ | 68％ | 76％ | 82％ | 85％ |
| Example 4 | 8％ | 18％ | 30％ | 41％ | 53％ | 62％ | 70％ | 76％ | 79％ |
| Example 5 | 25％ | 34％ | 48％ | 59％ | 71％ | 80％ | 88％ | 94％ | 97％ |
| Example 13 | 16％ | 26％ | 39％ | 50％ | 62％ | 71％ | 80％ | 85％ | 88％ |
| Comparative example 1 | 10％ | 18％ | 26％ | 34％ | 42％ | 50％ | 58％ | 65％ | 71％ |
| Comparative example 2 | 12％ | 18％ | 27％ | 34％ | 43％ | 51％ | 59％ | 66％ | 72％ |
| Comparative example 3 | 12％ | 18％ | 27％ | 34％ | 42％ | 49％ | 57％ | 63％ | 68％ |
| Comparative example 4 | 11％ | 17％ | 26％ | 33％ | 42％ | 49％ | 58％ | 65％ | 70％ |
As can be seen from the results of the methodological investigation in table 1 and the results of the detection of the release rate in table 2, the method for detecting the release rate of pramipexole dihydrochloride sustained release tablets provided in examples 1 to 3 enables the pramipexole dihydrochloride sustained release tablets to achieve complete release (the release rate is greater than 85%) in the release rate experiment process, and meets the requirements of the chinese pharmacopoeia and the guiding principles in the aspects of system applicability, specificity, repeatability (precision), recovery rate, stability and the like.
From the results of the comparison of the release rates of example 1 and comparative examples 1 to 4, it is found that the addition of cetyltrimethylammonium bromide to the dissolution and dissolution medium can improve the situation that the complete release of the drug is difficult due to the swelling of hypromellose with high viscosity, as compared with tween-80, sodium dodecylsulfonate and disodium laurylsulfosuccinate monoester.
According to the results of the release degrees of the embodiment 1 and the embodiments 4-5, the addition amount of the cetyl trimethyl ammonium bromide has an important effect on the complete release of the drug, the release is too fast due to the excessive addition amount of the cetyl trimethyl ammonium bromide, and the dissolution method has no distinguishing force and influences the test of the release degree; if the amount of the drug is too small, the drug cannot be completely released (release rate > 85%).
In conclusion, the invention provides a method for detecting the release degree of a pramipexole dihydrochloride sustained-release tablet, wherein a dissolution medium in the detection method consists of water, buffer salt and hexadecyl trimethyl ammonium bromide, and the release degree of the pramipexole dihydrochloride sustained-release tablet is analyzed by adopting high performance liquid chromatography. The dissolution medium in the determination method can improve the release amount of the pramipexole dihydrochloride sustained-release tablets in the release rate experiment process, so that the pramipexole dihydrochloride sustained-release tablets can be completely released (the release rate is more than 85%) in the release rate experiment process. The purpose of analysis is achieved by developing proper chromatographic conditions, and the detection method has the advantages of short analysis time, strong anti-interference performance and high sensitivity.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are only exemplary embodiments of the present invention, and are not intended to limit the present invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method for detecting the release rate of pramipexole dihydrochloride sustained-release tablets is characterized by comprising the following steps: dissolving the pramipexole dihydrochloride sustained-release tablets in a dissolving medium containing hexadecyl trimethyl ammonium bromide, and measuring the release degree of the pramipexole dihydrochloride sustained-release tablets by adopting high performance liquid chromatography.
2. The method for detecting the release rate of pramipexole dihydrochloride sustained release tablets according to claim 1, wherein the dissolution medium comprises cetyl trimethyl ammonium bromide and phosphate buffer;
preferably, the mass ratio of the cetyl trimethyl ammonium bromide to the phosphate buffer solution is (0.005-0.015): 100;
preferably, the phosphate buffer comprises the following components in parts by weight: 0.67-0.69 part of monopotassium phosphate, 0.088-0.092 part of sodium hydroxide, 0.01-1 part of pH regulator and 98-100 parts of water;
preferably, the pH adjusting agent comprises sodium hydroxide and/or phosphoric acid;
preferably, the pH of the phosphate buffer is 6.6-7.0.
3. The method for detecting the release rate of pramipexole dihydrochloride sustained release tablets according to claim 1 or 2, wherein the dissolution is specifically performed by: taking the pramipexole dihydrochloride sustained-release tablets, adopting a paddle method to dissolve the pramipexole dihydrochloride sustained-release tablets in a dissolving medium containing hexadecyl trimethyl ammonium bromide, and then sampling to obtain a test sample solution;
preferably, the volume of the dissolution medium is 890-910mL, the dissolution temperature is 35-38 ℃, and the dissolution rotation speed is 75-100 rpm;
preferably, sampling is carried out after 1-24h of dissolution;
preferably, the test solution is further subjected to filtration and/or centrifugation;
preferably, the pore size of the filtration is 0.22-0.45 μm;
preferably, the filter membrane material used for filtration comprises a water-based filter membrane and/or a nylon filter membrane;
preferably, the rotating speed of the centrifugation is 3000-.
4. The method for detecting the release rate of pramipexole dihydrochloride sustained release tablets according to any one of claims 1 to 3, wherein octadecylsilane chemically bonded silica is used as a filler in a chromatographic column of the high performance liquid chromatography;
preferably, the specification of the chromatographic column of the high performance liquid chromatography is (100-.
5. The method for detecting the release rate of pramipexole dihydrochloride sustained release tablets according to any one of claims 1 to 4, wherein the mobile phase of the high performance liquid chromatography comprises phosphate buffer containing octane sulfonate and acetonitrile;
preferably, the volume ratio of the phosphate buffer solution containing octane sulfonate to acetonitrile is (71-75): (25-29);
preferably, the octane sulfonate is sodium octane sulfonate;
preferably, the addition amount of the octane sulfonate accounts for 0.49-0.51% of the total mass of the phosphate buffer solution;
preferably, the pH of the phosphate buffer containing octane sulfonate is 2.8-3.2;
preferably, the phosphate buffer comprises the following components in parts by weight: 0.89-0.93 part of monopotassium phosphate, 0.02-0.15 part of phosphoric acid and 98-100 parts of water.
6. The method for detecting the release rate of pramipexole dihydrochloride sustained release tablets according to any one of claims 1 to 5, wherein the flow rate of the high performance liquid chromatography is 1.4 to 1.6 mL/min.
7. The method for detecting the release rate of pramipexole dihydrochloride sustained release tablets according to any one of claims 1 to 6, wherein the analysis time of the high performance liquid chromatography is 4 to 6 min.
8. The method for detecting the release rate of pramipexole dihydrochloride sustained release tablets according to any one of claims 1 to 7, wherein the column temperature of the high performance liquid chromatography is 38-42 ℃.
9. The method for detecting the release rate of the pramipexole dihydrochloride sustained release tablets according to any one of the claims 1 to 8, wherein the detection wavelength of the high performance liquid chromatography is 260-264 nm;
preferably, the sample injection volume of the high performance liquid chromatography is 98-102 μ L.
10. The method for detecting the release rate of pramipexole dihydrochloride sustained release tablets according to any one of claims 1 to 9, characterized in that the method comprises the following steps:
(1) dissolution of the sample: taking the pramipexole dihydrochloride sustained-release tablets, adopting a paddle method to dissolve in a dissolution medium containing hexadecyl trimethyl ammonium bromide, then sampling, filtering and/or centrifuging, and sampling at dissolution time points of 1h, 2h, 4h, 6h, 9h, 12h, 16h, 20h and 24h respectively to obtain test solution at different time points;
wherein the mass ratio of the cetyl trimethyl ammonium bromide to the phosphate buffer solution is (0.005-0.015): 100; the volume of the dissolution medium is 890-910mL, the dissolution temperature is 35-38 ℃, and the dissolution rotation speed is 75-100 rpm;
(2) and (3) detection of the sample: detecting the test solution at different time points by adopting high performance liquid chromatography, and calculating to obtain the release degree;
the chromatographic column of the high performance liquid chromatography takes octadecylsilane chemically bonded silica as a filler, and the specification of the chromatographic column of the high performance liquid chromatography is (100) and 150mm multiplied by (3-4.6mm) and 4-5 mu m; the mobile phase comprises phosphate buffer solution containing octane sulfonate and acetonitrile in a volume ratio of (71-75) to (25-29); the flow rate of the high performance liquid chromatography is 1.4-1.6mL/min, the analysis time is 4-6min, the column temperature is 38-42 ℃, the detection wavelength is 260-264nm, and the sample injection volume is 98-102 mu L.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115128184A (en) * | 2022-06-20 | 2022-09-30 | 上海橡实化学有限公司 | Method for determining content of thiourea in pramipexole dihydrochloride raw material by using HPLC (high performance liquid chromatography) external standard method |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951853A (en) * | 2016-10-17 | 2018-04-24 | 四川海思科制药有限公司 | A kind of body of Pramipexole dihydrochloride sustained release pharmaceutical composition and preparation method thereof |
| CN110133134A (en) * | 2019-05-17 | 2019-08-16 | 南通联亚药业有限公司 | A kind of analysis method measuring Quetiapine fumarate sustained-release tablets release |
| CN111721849A (en) * | 2019-03-23 | 2020-09-29 | 齐鲁制药(海南)有限公司 | Analysis method for determining content of main drug in pramipexole dihydrochloride sustained-release tablets |
| CN112704668A (en) * | 2021-01-12 | 2021-04-27 | 石药集团中奇制药技术（石家庄）有限公司 | Pramipexole dihydrochloride sustained-release composition |
-
2021
- 2021-12-21 CN CN202111574460.1A patent/CN114137130A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951853A (en) * | 2016-10-17 | 2018-04-24 | 四川海思科制药有限公司 | A kind of body of Pramipexole dihydrochloride sustained release pharmaceutical composition and preparation method thereof |
| CN111721849A (en) * | 2019-03-23 | 2020-09-29 | 齐鲁制药(海南)有限公司 | Analysis method for determining content of main drug in pramipexole dihydrochloride sustained-release tablets |
| CN110133134A (en) * | 2019-05-17 | 2019-08-16 | 南通联亚药业有限公司 | A kind of analysis method measuring Quetiapine fumarate sustained-release tablets release |
| CN112704668A (en) * | 2021-01-12 | 2021-04-27 | 石药集团中奇制药技术（石家庄）有限公司 | Pramipexole dihydrochloride sustained-release composition |
Non-Patent Citations (2)
| Title |
|---|
| 丛佳亮 等: "表面活性剂对疏水片面润湿性的调节及其对崩解和药物释放的影响" * |
| 张利锋 等: "盐酸普拉克索双相缓释胶囊的制备及体内外评价" * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115128184A (en) * | 2022-06-20 | 2022-09-30 | 上海橡实化学有限公司 | Method for determining content of thiourea in pramipexole dihydrochloride raw material by using HPLC (high performance liquid chromatography) external standard method |
| CN115128184B (en) * | 2022-06-20 | 2024-05-03 | 山东华泰新材料技术研发有限公司 | Method for determining thiourea content in pramipexole dihydrochloride raw material by using HPLC external standard method |
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Address after: 226009 No. 1, Guangxing Road, comprehensive free trade zone, economic and Technological Development Zone, Nantong City, Jiangsu Province Applicant after: Nantong Lianya Pharmaceutical Co.,Ltd. Address before: 226009 No. 1, Guangxing Road, comprehensive free trade zone, economic and Technological Development Zone, Nantong City, Jiangsu Province Applicant before: NOVAST LABORATORIES (CHINA) Ltd. |