Detection method for determining crystal form of fumaric acid Vonoprazan tablet by X-ray diffraction method

Abstract

The invention relates to the technical field of pharmaceutical analysis, and discloses a detection method for measuring the crystal form of a fumaric acid Vonorazan tablet by an X-ray diffraction method, which comprises the fumaric acid Vonorazan tablet and bulk drugs and auxiliary materials thereof, and is characterized in that the X-ray diffraction method is adopted to detect the crystal form of the fumaric acid Vonorazan tablet and the bulk drugs and the auxiliary materials thereof, and the X-ray diffraction method is adopted to detect the crystal form of the fumaric acid Vonorazan tablet and the bulk drugs and the auxiliary materials thereof. Comprising the following steps: step 1, preparing a test sample: grinding a fumaric acid Vonoprazan tablet into powder, sieving with a 100-mesh sieve, taking a proper amount of powder on a zero-background frame, flattening with a glass sheet, and putting into an instrument; according to the detection method for determining the crystal form of the fumaric acid vonorbitan tablet through the X-ray diffraction method, the detection method which is easy to operate, effective and universal can be provided for the crystal forms of the fumaric acid vonorbitan tablet and raw materials and auxiliary materials of the fumaric acid vonorbitan tablet, detection parameters of an X-ray powder diffractometer are limited, the crystal forms of the fumaric acid vonorbitan tablet and raw materials and auxiliary materials of the fumaric acid vonorbitan tablet are detected, and the detection accuracy is high. The specificity, the repeatability, the intermediate precision and the durability are good.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical analysis, and specifically provides a detection method for determining the crystal form of vonoprazan fumarate tablets by X-ray diffraction method. Background Art

[0002] Vonoprazan fumarate tablets are potassium ion-competitive acid blockers (P-CAB), also known as proton pump inhibitors (hereinafter referred to as: PPI). Existing PPIs such as lansoprazole are converted into active metabolites under acidic conditions. This metabolite specifically inhibits the H+ / K+-ATPase in gastric mucosal parietal cells, thereby blocking the final step of gastric acid secretion. This product exerts its effect in the form of the original drug without the activation of acid. It mainly competitively and reversibly binds to inhibit K+ and H+ / K+-ATPase, and can stay in gastric parietal cells for a long time, thereby rapidly inhibiting gastric acid secretion.

[0003] A product named Wakix, an original research imported preparation, has become the first approved potassium ion-competitive acid blocker to enter the market, providing a new option for clinical use in the treatment of reflux esophagitis and will greatly improve the quality of life of patients with reflux esophagitis.

[0004] Although there are already clinical drugs on the market, there is no corresponding detection method for the crystal form of vonoprazan fumarate tablets, and thus the effective parameters of the crystal form of vonoprazan fumarate tablets cannot be understood.

[0005] Based on this, it is necessary to propose a detection method for determining the crystal form of vonoprazan fumarate tablets by X-ray diffraction method. Summary of the Invention

[0006] Aiming at the deficiencies of the prior art, the present invention provides a detection method for determining the crystal form of vonoprazan fumarate tablets by X-ray diffraction method, which has the advantage of being able to effectively detect the crystal form of vonoprazan fumarate tablets, and solves the problems raised in the background art.

[0007] The present invention provides the following technical solution: A detection method for determining the crystal form of vonoprazan fumarate tablets by X-ray diffraction method, including vonoprazan fumarate tablets and their raw materials, excipients:

[0008] The crystal forms of vonoprazan fumarate tablets and their raw materials and excipients are detected by X-ray diffraction method; the following steps are included:

[0009] Step 1: Preparation of test sample: Take one vonoprazan fumarate tablet, grind it into powder, pass through a 100-mesh sieve, take an appropriate amount of powder on a zero-background holder, flatten it with a glass slide and then place it in the instrument.

[0010] Step 2: Detection and result analysis: Set the X-ray powder diffractometer according to the instrument parameters, and detect and analyze the test sample.

[0011] Preferably, the detection conditions of the X-ray powder diffractometer are Cu target, voltage 30 KV, current 10 mA, and rotation speed 20 / min.

[0012] Preferably, the detection conditions of the X-ray powder diffractometer: the scanning range 2θ is 3° to 60°.

[0013] Preferably, the detection conditions of the X-ray powder diffractometer are step size: 0.018° to 0.022°, and step time 0.28 to 0.32 s.

[0014] Compared with the prior art, the present invention has the following beneficial effects:

[0015] This detection method for determining the crystal form of voruprazan fumarate tablets by X-ray diffraction can provide a simple, effective, and general detection method for the crystal forms of voruprazan fumarate tablets and their raw materials and excipients. By defining the detection parameters of the X-ray powder diffractometer, the present invention detects the crystal forms of voruprazan fumarate tablets and their raw materials and excipients, and the present invention has good specificity, repeatability, intermediate precision, and durability, and the detection operation process is simple and easy to operate. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention, and those of ordinary skill in the art can also obtain other drawings based on these drawings without creative efforts.

[0017] Figure 1 XRD pattern of the test sample (batch number: batch 202312001) of the present invention;

[0018] Figure 2 XRD pattern of the test sample (batch number: batch 202312002) of the present invention;

[0019] Figure 3 XRD pattern of the test sample (batch number: batch 202312003) of the present invention;

[0020] Figure 4 XRD pattern of the test sample (batch number: batch 12404957) of the present invention;

[0021] Figure 5 Overlay diagram of voruprazan fumarate tablets, voruprazan fumarate raw materials, and voruprazan fumarate excipients of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0022] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0023] Please refer to Figure 1 、 Figure 2 、 Figure 3 、 Figure 4 and Figure 5 , a detection method for determining the crystal form of voruprazan fumarate tablets by X-ray diffraction method, including voruprazan fumarate tablets and their raw materials, excipients, as follows:

[0024] The crystal forms of voruprazan fumarate tablets and their raw materials and excipients are detected by the X-ray diffraction method; the following steps are included:

[0025] Step 1: Preparation of test sample: Take one voruprazan fumarate tablet, grind it into powder, pass it through a 100-mesh sieve, take an appropriate amount of the powder on a zero-background holder, flatten it with a glass slide and then place it in the instrument.

[0026] Step 2: Detection and result analysis: Set the X-ray powder diffractometer according to the instrument parameters, and detect and analyze the test sample.

[0027] As a preferred technical solution of the present invention, the detection conditions of the X-ray powder diffractometer are Cu target, voltage 30 KV, current 10 mA, and rotation speed 20 / min.

[0028] As a preferred technical solution of the present invention, the detection conditions of the X-ray powder diffractometer are: the scanning range 2θ is 3° to 60°.

[0029] As a preferred technical solution of the present invention, the detection conditions of the X-ray powder diffractometer are step size: 0.018° to 0.022°, and step time 0.28 to 0.32 s.

[0030] Example 1 Crystal form detection of voruprazan fumarate tablets:

[0031] 1. Instrument equipment and test sample

[0032] 1.1 Instrument: Powder X-ray diffractometer, manufactured by Bruker, model D2 PHASER.

[0033] 1.2 Test sample: Voruprazan fumarate tablets, specification 20 mg, manufactured by Harbin Pharmaceutical Group Technology Center / Takeda Japan, voruprazan fumarate raw material, manufactured by Chongqing Bonten, voruprazan fumarate excipient, manufactured by Harbin (Beijing) Biotech Co., Ltd.

[0034] 2. Detection Conditions

[0035] Table 1 Detection Parameters

[0036]

[0037] 3. Test Method

[0038] Take one tablet of vonoprazan fumarate (batch numbers: 12404957 / 202312001 / 202312002 / 202312003), grind it into powder, pass it through a 100-mesh sieve, take an appropriate amount of the powder on a zero-background holder, flatten it with a glass slide and then place it in the instrument. Set the instrument parameters according to Table 1 and detect the test sample.

[0039] 4. Detection Results

[0040] Table 2 Detection Results of the Crystal Form of the Test Sample

[0041]

[0042]

[0043] Vonoprazan fumarate tablets (batch numbers: 12404957, 202312001, 202312002, 202312003) all have specific diffraction peaks, indicating that the sample is a crystalline powder.

[0044] Methodology Verification of Example 2

[0045] 1. The instrument equipment and the test sample are the same as those in Example 1.

[0046] 2. The detection conditions are the same as those in Example 1.

[0047] 3. Specificity

[0048] 3.1 Test Method

[0049] Take one tablet of vonoprazan fumarate (batch number: 202312003), grind it into powder, pass it through a 100-mesh sieve, take an appropriate amount of the powder on a zero-background holder, flatten it with a glass slide and then place it in the instrument. Set the instrument parameters according to Table 1 and detect the test sample. Take appropriate amounts of vonoprazan fumarate raw material drug and vonoprazan fumarate excipient powder respectively and detect them in the same way.

[0050] 3.2 Detection Results

[0051] Table 3 Specificity Results (Comparison Table of the Main Characteristic Diffraction Peaks between Vonoprazan Fumarate Tablets and Vonoprazan Fumarate Raw Material Drug)

[0052]

[0053]

[0054] 4. Repeatability

[0055] 4.1 Test method

[0056] Technician A took one tablet of vorolaner fumarate tablets (batch number: 202312003), ground it into powder, passed it through a 100-mesh sieve, took an appropriate amount of the powder on a zero-background holder, flattened it with a glass slide and then placed it in the instrument. According to the instrument parameters set in Table 1, the test sample was detected. Six samples were prepared in the same way and each was detected once.

[0057] 4.2 Test results

[0058] Table 4 Repeatability results (Comparison table of the main characteristic diffraction peaks of vorolaner fumarate tablets in 6 repetitions)

[0059]

[0060]

[0061] 5. Intermediate precision

[0062] 5.1 Test method

[0063] Technician B took one tablet of vorolaner fumarate tablets (batch number: 202312003) on different dates, ground it into powder, passed it through a 100-mesh sieve, took an appropriate amount of the powder on a zero-background holder, flattened it with a glass slide and then placed it in the instrument. According to the instrument parameters set in Table 1, the test sample was detected. Six samples were prepared in the same way and each was detected once.

[0064] 5.2 Test results

[0065] Table 5 Intermediate precision results - 1 (Comparison table of the main characteristic diffraction peaks of vorolaner fumarate tablets in 6 intermediate precision tests - 1)

[0066]

[0067]

[0068] Table 6 Intermediate precision - 2 (Comparison table of the main characteristic diffraction peaks of vorolaner fumarate tablets in 6 intermediate precision tests - 2)

[0069]

[0070] 6. Robustness

[0071] 6.1 Test method

[0072] Change the experimental parameters according to the following table. For each parameter change, take one tablet of Vorapaxar Tablets (batch number: 202312003), grind it into powder, pass it through a 100-mesh sieve, take an appropriate amount of the powder on a zero-background holder, flatten it with a glass slide, and then place it in the instrument. Set the instrument parameters according to Table 1 and test the test sample.

[0073] Table 7 Investigation Conditions for the Durability Test

[0074]

[0075] 6.2 Test Results

[0076] Table 8 Durability Results

[0077]

[0078] Although the embodiments of the present invention have been shown and described, those of ordinary skill in the art can understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for detecting the crystal form of vonoprazan fumarate tablets by X-ray diffraction, comprising vonoprazan fumarate tablets and their raw materials and excipients, characterized in that: The method of using X-ray diffraction to detect the crystal form of vonoprazan fumarate tablets and its raw materials and excipients comprises the following steps: Step 1: Prepare the sample: Take one vonolase fumarate tablet, grind it into powder, pass it through a 100-mesh sieve, take an appropriate amount of powder on the zero background rack, flatten it with a glass slide and put it into the instrument; Step 2: Detection and result analysis: Set the X-ray powder diffractometer according to the instrument parameters and perform detection and analysis on the test sample.

2. The method for determining the crystal form of vonoprazan fumarate tablets by X-ray diffraction according to claim 1, characterized in that: The detection conditions of the X-ray powder diffractometer are Cu target, voltage 30KV, current 10mA, and rotation speed 20 / min.

3. The method for determining the crystal form of vonoprazan fumarate tablets by X-ray diffraction according to claim 2, characterized in that: The detection conditions of the X-ray powder diffractometer are as follows: the scanning range 2θ is 3° to 60°.

4. The method for determining the crystal form of vonoprazan fumarate tablets by X-ray diffraction according to claim 1, characterized in that: The detection conditions of the X-ray powder diffractometer are as follows: step length: 0.018° to 0.022°, step time: 0.28 to 0.32 s.

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