In-vitro dissolution method of mirabegron sustained release tablet

An in vitro dissolution and mirabegron technology, applied in the direction of testing pharmaceutical preparations, instruments, measuring devices, etc., can solve the problems of no high discrimination, inability to truly simulate the absorption trough conditions to reflect the release in vivo, and one-sided differences, etc., to achieve Save R&D costs, reduce R&D risks, and improve the success rate

Pending Publication Date: 2022-08-05
HUNAN HUIZE BIO PHARMA CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are few domestic reports on its dissolution / release rate and the correlation between in vivo and in vitro, and relevant reports (Liang Shengqun, Zou Meijuan. Consistency evaluation of in vitro dissolution of self-made Mirabegron sustained-release tablets and reference preparations[J]. China Prescription Drugs, 2017, 15(8): 32-34; Ni Dongsheng, Sun Jinglong, Ding Gang, et al. Evaluation of in vitro release consistency between self-developed Mirabegron sustained-release tablets and reference preparations[J]. 2020,40(6):1058-1068; Wang Lishuang, Chen Qiu, Zhang Xiaohua. Development and application of optical fiber release detection method for Mirabegron sustained-release tablets[J]. Shandong Chemical Industry, 2022,51(7):126-129 .) Generally, the dissolution test of the self-developed preparation and the reference preparation is carried out under four curves by using the basket method (that is, the four solutions of pH 1.2 hydrochloric acid solution, pH 4.5 acetate buffer solution, pH 6.8 phosphate buffer solution and water are used as Dissolution test with dissolution medium), using similar factors for similarity comparison, but for the traditional dissolution method, the movement of the mechanical device is single and cannot approximate the dynamic process of simulating the laminar flow state and fluid mechanics of the gastrointestinal tract in vivo, and cannot truly simulate absorption leakage. Tank conditions and reflect the in vivo release situation, even if the dissolution trend is consistent under the recommended method or the four curves, the similarity factor is higher than 50, the in vitro dissolution is far from the in vivo results; no high discrimination

Method used

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  • In-vitro dissolution method of mirabegron sustained release tablet

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Optimize the dissolution medium.

[0072] Mirabegron sustained-release tablet reference preparation was under two different media conditions of water and pH 6.8 phosphate buffer, and the flow rate of the dissolution medium was 4 mL / min; The dissolution medium was internally circulated at a flow rate of 100 mL / min for 8 h, and the dissolution test was conducted over a period of 8 h.

[0073] The concentration of mirabegron samples at each time point was detected by high performance liquid chromatography, and the dissolution curves and in vitro and in vivo correlation curves were obtained.

[0074] The test results are as Figure 1~2The test results show that at 480 min, the cumulative dissolution rates of the reference preparation under two different dissolution media conditions of water and pH 6.8 phosphate buffer are 89.87% and 97.50%, respectively. The dissolution rate was closer to the in vivo absorption rate (85.73%). From the in vitro and in vivo correlation cur...

Embodiment 2

[0076] The dissolution medium flow rate is optimized.

[0077] According to the conclusion of Example 1, when water is used as the dissolution medium, Mirabegron sustained-release tablets show better in vitro and in vivo correlation. Therefore, in this example, water is used as the dissolution medium, and the flow rate of the dissolution medium is 4 Or 6 mL / min, the dissolution process is the natural swelling in the 0~1.5 h, the internal circulation of the dissolution medium at the flow rate of 100 mL / min in the 1.5~8 h, and the dissolution test is carried out for 8 h. Correlation.

[0078] The test results are as Figure 3~4 As shown, the test results show that at 480 min, the cumulative dissolution rates of the reference preparation under the two different conditions of dissolution medium flow rate of 4 mL / min and 6 mL / min are 89.87% and 100.15%, respectively. At 4 mL / min, the cumulative dissolution rate was closer to the in vivo absorption rate (85.73%). From the in vitr...

Embodiment 3

[0080] According to the optimal test conditions of Examples 1 and 2, the dissolution process was further optimized.

[0081] The reference preparation of mirabegron sustained-release tablets used water as the dissolution medium, and the flow rate of the dissolution medium was 4 mL / min. The effects of different dissolution processes on the correlation between in vitro and in vivo were compared;

[0082] First, tests were performed under two dissolution conditions:

[0083] A) The dissolution medium is internally circulated at a flow rate of 100 mL / min from 0 to 6 h;

[0084] B) Natural swelling in the 0~1.5 h, and internal circulation of the dissolution medium at a flow rate of 100 mL / min in the 1.5~6 h.

[0085] The test results are as Figure 5 As shown, at 360 min, the cumulative dissolution percentages in vitro under the dissolution conditions of A) and B) were 80.32% and 75.10%, respectively, both of which were close to the in vivo absorption percentage (77.82%) at this ...

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Abstract

The invention belongs to the technical field of pharmaceutical analysis, and particularly discloses an in-vitro dissolution method of mirabegron sustained release tablets. A flow cell method is adopted, a dissolution medium is conveyed to a dissolution container through a constant flow pump, the medicine is continuously pumped out of the dissolution container along with the dissolution medium at the same constant flow speed in the swelling and erosion processes, and sampling is conducted at intervals at a fixed time point; and detecting the mirabegron sample concentration at each time point by using a high performance liquid chromatograph to obtain a mirabegron dissolution curve and an in-vivo and in-vitro correlation curve, and predicting the bioequivalence of the tested preparation and the reference preparation. The dissolution method adopted by the invention can truly simulate in-vivo release and absorption processes, realizes in-vivo and in-vitro correlation of drugs, and combines f2 factors to doubly analyze preparation differences, so that quality differences and process differences between a reference preparation and different tested preparations can be effectively distinguished, and similarity and quality consistency evaluation of mirabegron sustained release preparations is realized.

Description

technical field [0001] The invention relates to the technical field of drug analysis, in particular to an in vitro dissolution method of mirabegron sustained-release tablets. Background technique [0002] Mirabellon, molecular formula C 21 H 24 N 4 O 2 S, is a novel and specific β3 adrenergic receptor agonist. It stimulates adenylate cyclase (AC) and produces cAMP to induce relaxation of the detrusor muscle of the bladder, thereby promoting bladder filling and increasing bladder It is used to treat overactive bladder including symptoms of urinary incontinence, urgency and frequent urination. Mirabegron sustained-release tablets are rapidly absorbed after oral administration in the fasting state, reaching a peak concentration in about 4 hours, but the bioavailability is low; it is widely distributed in the body, and the binding rate to human plasma protein reaches 71%; The elimination half-life is as long as 50 h, and the urinary excretion is dose-dependent. Some are exc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/15G01N30/02G01N30/06G01N30/30G01N30/32G01N30/34G01N30/74G01N30/86
CPCG01N33/15G01N30/02G01N30/06G01N30/30G01N30/32G01N30/34G01N30/74G01N30/8675G01N2030/324
Inventor 冀闪易木林
Owner HUNAN HUIZE BIO PHARMA CO LTD
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