阅读说明：本技术 一种盐酸贝尼地平片溶出度的检测方法 (Method for detecting dissolution rate of benidipine hydrochloride tablets ) 是由 王熙红 杨淑萍 林丽丽 刘鑫 于 2019-10-14 设计创作，主要内容包括：本发明涉及一种盐酸贝尼地平片溶出度的检测方法,更能模拟体现环境,反映出样品的质量差异,且解决了现有盐酸贝尼地平片溶出度的检测方法存在因为各种吸附及不同程度地盐酸贝尼地平分解原因出现的检测数据结果偏低且整体差异比较大的情况发生的技术问题。本发明提供一种盐酸贝尼地平片溶出度的检测方法,包括以下步骤：取盐酸贝尼地平片,照溶出度测定法(中国药典2015版四部通则0931第二法,使用沉降篮),以氯化钠的盐酸溶液900ml为溶出介质,转速为每分钟50转,依法操作,经45min时,使用PEEK材质的取样针取溶液适量,离心,取上清液作为供试品溶液。本发明应用于盐酸贝尼地平片溶出度的检测。(The invention relates to a method for detecting dissolution rate of benidipine hydrochloride tablets, which can simulate and embody the environment, reflect the quality difference of samples and solve the technical problems of low detection data result and large overall difference caused by various adsorption and different degrees of decomposition of benidipine hydrochloride in the conventional method for detecting dissolution rate of benidipine hydrochloride tablets. The invention provides a method for detecting dissolution rate of benidipine hydrochloride tablets, which comprises the following steps: taking benidipine hydrochloride tablets, according to a dissolution determination method (a second method of 0931 in the four parts of the pharmacopoeia 2015 edition, China general regulations, using a settling basket), taking 900ml of sodium chloride hydrochloric acid solution as a dissolution medium, rotating at 50 revolutions per minute, operating according to the method, taking a proper amount of solution by using a sampling needle made of PEEK material after 45min, centrifuging, and taking supernatant as a sample solution. The invention is applied to the detection of the dissolution rate of the benidipine hydrochloride tablets.)

1. The method for detecting the dissolution rate of the benidipine hydrochloride tablets is characterized by comprising the following steps of: taking benidipine hydrochloride tablets, according to a dissolution determination method (a second method of 0931 in the four parts of the pharmacopoeia 2015 edition, China general regulations, using a settling basket), taking 900ml of sodium chloride hydrochloric acid solution as a dissolution medium, rotating at 50 revolutions per minute, operating according to the method, taking a proper amount of solution by using a sampling needle made of PEEK material after 45min, centrifuging, and taking supernatant as a sample solution.

2. The method for detecting dissolution rate of benidipine hydrochloride tablets according to claim 1, wherein the preparation method of the dissolution medium comprises the following steps: 2g of sodium chloride is taken, 7ml of hydrochloric acid is added, and water is added to 1000 ml.

3. The method for detecting the dissolution rate of the benidipine hydrochloride tablet as claimed in claim 1, further comprising the steps of:

the detection method comprises the following steps:

(1) preparing a reference substance solution: dissolving a proper amount of benidipine hydrochloride reference substance by using a mobile phase, and quantitatively diluting to prepare a solution containing about 0.44mg in each 1ml of the benidipine hydrochloride reference substance as a reference substance storage solution; precisely measuring 1ml of reference stock solution, placing in a 50ml measuring flask, diluting to scale with dissolution medium, and shaking to obtain reference solution;

(2) measuring by high performance liquid chromatography, and separating with chromatographic column using octadecylsilane chemically bonded silica as filler; using 0.05mol/L potassium dihydrogen phosphate solution (pH is adjusted to 3.0 by phosphoric acid) -acetonitrile (55: 45) as a mobile phase; detecting wavelength at 237nm, flow rate at 1.0ml/min, column temperature at 25 deg.C, calculating theoretical plate number at least 3000 according to benidid hydrochloride flat peak, precisely measuring sample solution and reference solution each 50 μ l, respectively injecting into liquid chromatograph, and recording chromatogram; the elution amount of each tablet was calculated by peak area according to the external standard method.

4. The method for detecting the dissolution rate of benidipine hydrochloride tablets according to claim 1, wherein the centrifugation is carried out at 4000 rpm for 5 min.

5. The method of claim 1, wherein the chromatography column is Kromasil C18250 x 4.6mm, 5 μm or performance equivalent chromatography column.

6. The method for detecting the dissolution rate of benidipine hydrochloride tablets as claimed in claim 1, wherein the sampling needle made of PEEK is used for sampling the solution.

Technical Field

The invention relates to the technical field of pharmacy, in particular to a method for detecting dissolution rate of benidipine hydrochloride tablets.

Background

Benidipine hydrochloride belongs to dihydropyridine calcium ion antagonists, and expands blood vessels by binding to dihydropyridine receptors that block cell membrane potential-dependent calcium ion channels, and preventing calcium ion influx into cells. Benidipine hydrochloride is widely used as a therapeutic drug for hypertension, renal essential hypertension, angina pectoris, and the like because it is safe and effective.

The dissolution rate result of the benidipine hydrochloride tablet is a key detection standard for investigating the in-vitro simulated bioavailability test of the benidipine hydrochloride tablet and is also the most important detection index for investigating the quality standard of the benidipine hydrochloride tablet preparation. However, the existing detection technology has the following problems:

(1) the dissolution method of the benidipine hydrochloride tablets in China at present comprises the following steps: according to a dissolution rate determination method (a third method of 0931 of the four general rules of the Chinese pharmacopoeia 2015 edition), the detection result is relatively high in accuracy and poor in high performance liquid chromatography.

(2) The benidipine hydrochloride tablet is an oral preparation, is digested and absorbed in the stomach, is acidic in the stomach environment, and should be dissolved in a similar dissolution medium; in addition, benidipine hydrochloride has poor water solubility and strong pH dependence, and the quality control of the daily dissolution rate cannot be carried out by selecting conventional solvents such as water and the like.

(3) The dissolution rate of benidipine hydrochloride tablets is detected in Japanese pharmacopoeia and dissolution liquid mostly specified in Chinese pharmacopoeia is filtered by a 0.45-micrometer filter membrane after being sampled, but the filter membrane adsorbs most active ingredients, and the quality difference among the filter membranes causes different adsorption degrees, thereby influencing the accuracy of the dissolution rate detection result.

(4) Benidipine hydrochloride belongs to dihydropyridine calcium ion antagonists, when dissolution is detected by a medium with pH of about 1, the benidipine hydrochloride can be decomposed by a stainless steel sampling needle of a dissolution instrument, the decomposition degrees are different, high performance liquid chromatography cannot be used for normal analysis, the dissolution result cannot be accurately detected, and misjudgment is caused.

(5) If the chromatographic conditions including the composition and proportion of the mobile phase, the flow rate, the type of the chromatographic column and the like are not properly selected, the problems of overlong analysis time, poor symmetry of chromatographic peaks and the like can be caused.

Disclosure of Invention

The invention aims to overcome the defects of the prior art, simulate the in-vivo environment according to the characteristics of benidipine hydrochloride, and develop a simple, quick, accurate and well-differentiated dissolution rate detection method; the method for detecting the dissolution rate of the benidipine hydrochloride tablet can effectively prevent the phenomenon of adsorption and decomposition of the benidipine hydrochloride tablet in a hydrochloric acid medium without using special substances, and is proved to be true by a methodology.

The technical scheme adopted by the invention for solving the technical problem is as follows:

a method for detecting dissolution rate of benidipine hydrochloride tablets comprises the following steps: taking benidipine hydrochloride tablets, according to a dissolution determination method (a second method of 0931 in the four parts of the pharmacopoeia 2015 edition, China general regulations, using a settling basket), taking 900ml of sodium chloride hydrochloric acid solution as a dissolution medium, rotating at 50 revolutions per minute, operating according to the method, taking a proper amount of solution by using a sampling needle made of PEEK material after 45min, centrifuging, and taking supernatant as a sample solution.

Preferably, the method of preparation of the dissolution medium: 2g of sodium chloride is taken, 7ml of hydrochloric acid is added, and water is added to 1000 ml.

Preferably, the method further comprises the following steps:

the detection method comprises the following steps:

(1) preparing a reference substance solution: dissolving a proper amount of benidipine hydrochloride reference substance by using a mobile phase, quantitatively diluting to prepare a solution containing about 0.44mg in each 1ml, taking the solution as a reference substance storage solution, precisely measuring 1ml of the reference substance storage solution, placing the solution in a 50ml measuring flask, diluting the solution to a scale by using a dissolution medium, and shaking the solution uniformly to obtain a reference substance solution;

(2) measuring by high performance liquid chromatography, and separating with chromatographic column using octadecylsilane chemically bonded silica as filler; using 0.05mol/L potassium dihydrogen phosphate solution (pH is adjusted to 3.0 by phosphoric acid) -acetonitrile (55: 45) as a mobile phase; detecting wavelength at 237nm, flow rate at 1.0ml/min, column temperature at 25 deg.C, calculating theoretical plate number at least 3000 according to benidid hydrochloride flat peak, precisely measuring sample solution and reference solution each 50 μ l, respectively injecting into liquid chromatograph, and recording chromatogram; the elution amount of each tablet was calculated by peak area according to the external standard method.

Preferably, the centrifugation is carried out at 4000 rpm for 5 min.

Preferably, the column is a Kromasil C18250X 4.6mm, 5 μm or equivalent performance column.

The invention has the beneficial effects that:

compared with the prior art, the method for detecting the dissolution rate of the benidipine hydrochloride tablets is simple to operate, special substances are not required to be used, the phenomenon that the benidipine hydrochloride tablets are dissolved out in a hydrochloric acid medium and adsorbed and decomposed can be effectively prevented, and the establishment of the method is verified through methodology.

Detailed Description

The present invention will be further described with reference to specific examples to assist understanding of the invention. The method used in the invention is a conventional detection method if no special provisions are made; the starting materials used, unless otherwise specified, are conventional commercial products.

Examples

A method for detecting dissolution rate of benidipine hydrochloride tablets comprises the following steps:

taking the product, according to a dissolution determination method (0931 second method of the general rule of four parts of the Chinese pharmacopoeia 2015 edition, using a settling basket), taking 900ml of hydrochloric acid solution of sodium chloride (2 g of sodium chloride, 7ml of hydrochloric acid and water till 1000 ml) as a dissolution medium, rotating at 50 r/min, operating according to the method, taking a proper amount of solution by using a sampling needle made of PEEK material after 45min, centrifuging (4000 r/min, 5 min), and taking supernatant as a sample solution;

taking another appropriate amount of benidipine hydrochloride as reference substance, dissolving with mobile phase, quantitatively diluting to obtain solution containing about 0.44mg per 1ml, using as reference substance stock solution, precisely measuring 1ml of reference substance stock solution, placing in a 50ml measuring flask, diluting to scale with dissolution medium, shaking, and using as reference substance solution.

Measuring by high performance liquid chromatography (0512 in the four-part general regulation of the Chinese pharmacopoeia 2015 edition), using octadecylsilane chemically bonded silica as filler (Kromasil C18250 × 4.6mm, 5 μm or chromatographic column with equivalent efficiency); using 0.05mol/L potassium dihydrogen phosphate solution (pH is adjusted to 3.0 by phosphoric acid) -acetonitrile (55: 45) as a mobile phase; the detection wavelength was 237nm, the flow rate was 1.0ml/min, and the column temperature was 25 ℃. The number of theoretical plates should not be less than 3000 calculated according to the benidid hydrochloride flat peak, precisely measuring the sample solution and the reference solution by 50 μ l each, injecting into a liquid chromatograph, and recording chromatogram.

The dissolution amount of each tablet is calculated by peak area according to an external standard method, the average value of the dissolution rate of the benidipine hydrochloride tablets is 92% of the marked amount, the RSD value is 0.56%, the dissolution rate of the benidipine hydrochloride tablets meets the specification and is in direct proportion to the content test result, and the establishment of the method is verified through methodology, so that no obvious adsorption occurs.

In conclusion, compared with the prior art, the method for detecting the dissolution rate of the benidipine hydrochloride tablets is simple to operate, can simulate the in-vivo environment better, reflects the mass difference of samples and has good differentiation force. And solves the problems of various adsorption and different degrees of decomposition of benidipine hydrochloride in the existing method for detecting the dissolution rate of the benidipine hydrochloride tablets. And the methodology was verified to be true.

However, the above description is only an embodiment of the present invention, and the scope of the present invention should not be limited by this, and all equivalent changes and modifications made in the claims of the present invention should be covered by the present invention.