A method for determining the content of hydroxypropyl cellulose

Abstract

The present invention relates to the technical field of drug detection, and particularly to a method for determining the content of hydroxypropyl cellulose. The detection method provided by the present invention comprises the following steps: weighing high-substituted hydroxypropyl cellulose, using water or a polar organic solvent as a solvent, preparing a hydroxypropyl cellulose solution, and diluting to obtain a series of hydroxypropyl cellulose reference solutions with different concentrations; taking a preparation sample, grinding, weighing the fine powder, extracting by water bath and preparing a corresponding test solution; detecting the series of hydroxypropyl cellulose reference solutions by HPLC-CAD method, and drawing a standard curve; determining the test solution with a target concentration by HPLC-CAD method and obtaining target peak information, and then calculating the content of hydroxypropyl cellulose in the test solution by the external standard curve method. The pretreatment steps of the present invention are simple, which can not only detect the content of hydroxypropyl cellulose, but also reflect the model difference; the detection results are accurate, precise and repeatable.

Description

Technical Field

[0001] The present invention relates to the technical field of drug detection, and particularly to a method for determining the content of hydroxypropyl cellulose. Background Art

[0002] In the process of generic drug research and development, it is necessary to conduct a detailed study on reference preparations. Although most excipients have no clinical activity, they will affect the performance of drug products, such as stability, hardness, dissolution rate, etc. Therefore, the reverse analysis of excipients in reference preparations and the determination of the type and content of excipients have important guiding significance for the research and development of generic drugs. As a macromolecular pharmaceutical excipient, hydroxypropyl cellulose has a molecular weight range from several thousand to several hundred megadaltons, and is a mixture of non-single components. It is mainly used as a binder and disintegrant, and is widely used in oral capsules and tablets, topical and transdermal absorption preparations.

[0003] Currently, the methods for determining the content of hydroxypropyl cellulose mainly refer to the General Rules of the Fourth Part of the Chinese Pharmacopoeia 2020 Edition. Usually, gas chromatography or volumetric method is used to determine the content of hydroxypropoxy groups. Since drug preparation products often have complex components, the sample treatment process is cumbersome, time-consuming, and the accuracy of the determination results is poor. In the existing determination methods, the volumetric method has a complex device, the reagent hydroiodic acid used in gas chromatography is highly corrosive, and the reference 2-iodopropane used is extremely volatile and prone to deterioration, and standardization is required before each determination. In addition, the existing technology can only determine the content of hydroxypropyl cellulose and cannot compare specific type differences. Summary of the Invention

[0004] The purpose of the present invention is to provide a method for determining the content of hydroxypropyl cellulose to solve the problems raised in the above background art.

[0005] The present invention is achieved through the following technical solutions:

[0006] A method for determining the content of hydroxypropyl cellulose includes the following steps:

[0007] S1. Weigh high-substituted hydroxypropyl cellulose, use water or polar organic solvent as a solvent to prepare a hydroxypropyl cellulose solution, and dilute it to obtain a series of hydroxypropyl cellulose reference solutions with different concentrations;

[0008] S2. Take a preparation sample containing the high-substituted hydroxypropyl cellulose in step S1 as an excipient, grind it, weigh the fine powder, extract it by water bath and prepare a corresponding test solution;

[0009] S3. Use HPLC-CAD method to detect the series of hydroxypropyl cellulose reference solutions obtained in step S1, obtain the peak area of hydroxypropyl cellulose in the reference solution, and perform standard curve fitting with the concentration of the reference solution;

[0010] S4. Determine the test solution with the target concentration by HPLC-CAD method, obtain the target peak information, and then calculate the content of hydroxypropyl cellulose in the test solution by the external standard curve method;

[0011] In the above steps, the HPLC-CAD method uses a chromatographic column filled with octadecylsilane-bonded silica gel.

[0012] As a further scheme of the present invention, the parameters of the HPLC-CAD method are specifically as follows: gradient elution is carried out in 0-20 min with an acetonitrile / methanol-water system as the mobile phase, wherein the volume percentage of the organic phase is 0-90%, the chromatographic column uses a Presto FF-C18 chromatographic column, CAD is used as the detector, the column temperature is 40-80 °C, and the flow rate is 0.3-0.8 mL / min.

[0013] As a further scheme of the present invention, in step S1, the content of the hydroxypropyl cellulose solution before dilution is 5 wt.%, and according to different types of hydroxypropyl cellulose used, the viscosities of the prepared hydroxypropyl cellulose solutions are 500 cps, 250 cps, and 100 cps respectively.

[0014] As a further scheme of the present invention, in step S1, the concentrations of the series of hydroxypropyl cellulose reference solutions are 3.775 μg / mL, 15.1 μg / mL, 37.75 μg / mL, 75.5 μg / mL, 113.25 μg / mL, and 151 μg / mL respectively.

[0015] Preferably, the polar organic solvent includes at least one of acetonitrile, methanol, ethanol, and isopropanol.

[0016] Compared with the prior art, the beneficial effects of the present invention are:

[0017] The present invention uses the HPLC-CAD method to not only detect the content of hydroxypropyl cellulose but also reflect the type differences. The pretreatment steps of the method provided by the present invention are simple, the detection results are accurate and precise, and it has repeatability. Description of the Drawings

[0018] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without creative efforts.

[0019] Figure 1 It is the standard curve graph of the hydroxypropyl cellulose reference solution of the present invention;

[0020] Figure 2 It is the detection spectrum of different types of hydroxypropyl cellulose of the present invention;

[0021] Figure 3 This is the detection spectrum of hydroxypropyl cellulose in different preparation samples of the present invention. Detailed implementation manners

[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. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0023] If there is no special indication, the reagents used in the embodiments can be easily obtained from commercial companies.

[0024] Example 1:

[0025] This embodiment provides a method for determining the content of hydroxypropyl cellulose, which specifically includes the following steps:

[0026] S1. Weigh different types of high-substituted hydroxypropyl cellulose and prepare a hydroxypropyl cellulose solution with a content of 5 wt.% using water or a polar organic solvent as the solvent. Since the influence of the solvent on the determination method of this embodiment is small, the above-mentioned polar organic solvents such as methanol, ethanol, or isopropanol do not affect the subsequent determination of the hydroxypropyl cellulose content.

[0027] According to the different types of hydroxypropyl cellulose used, the viscosities of the prepared hydroxypropyl cellulose solutions are 500 cps (type 1), 250 cps (type 2), and 100 cps (type 3) respectively; take the hydroxypropyl cellulose solution with a viscosity of 500 cps (type 1) and dilute it to obtain a series of hydroxypropyl cellulose reference solution with concentrations of 3.775 μg / mL, 15.1 μg / mL, 37.75 μg / mL, 75.5 μg / mL, 113.25 μg / mL, and 151 μg / mL respectively;

[0028] S2. Take preparation samples (preparation I and preparation II) from different manufacturers. Preparation I and preparation II belong to the same variety and all excipients are the same. Grind the preparation samples and weigh the fine powder, extract them in a water bath and prepare the corresponding test solution;

[0029] S3. Set the parameters of the HPLC-CAD method as follows: use an acetonitrile / methanol-water system as the mobile phase for gradient elution, where the volume percentage of the organic phase is 0-90%, and the specific gradient program is shown in Table 1; use a Presto FF-C18 chromatographic column, use CAD as the detector, the column temperature is 40-80 °C, and the flow rate is 0.3-0.8 mL / min;

[0030] Table 1:

[0031] Time Water Acetonitrile / Methanol 0 min 100％ 0％ 20 min 10％ 90％ 20.1 min 100％ 0％ 30 min 100％ 0％

[0032] The series of hydroxypropyl cellulose (Type 1) reference solutions obtained in Step S1 were detected by HPLC-CAD method to obtain the peak areas of hydroxypropyl cellulose in the reference solutions. The specific data are shown in Table 2, and a standard curve fitting was performed with the concentration of the reference solutions. The obtained standard curve formula is y = 0.1671x + 0.5421, R 2 = 0.9985. The fitted standard curve is shown in the appendix Figure 1 as shown. The results show that hydroxypropyl cellulose shows a good linear relationship within the concentration range;

[0033] Table 2:

[0034]

[0035] S4. The hydroxypropyl cellulose of Types 1-3, the reference solutions, and the test solutions of Preparation I and Preparation II were respectively determined by HPLC-CAD method to obtain the target peak information, and then the external standard curve method was used to calculate the content of hydroxypropyl cellulose in the test solutions. The test results are as Figures 2 - 3 shown. According to Figures 2 - 3 it can be seen that the hydroxypropyl cellulose of each type has great differences.

[0036] Take Preparation II with the same type and add a reference solution of hydroxypropyl cellulose (Type 1) with a set concentration. The content of hydroxypropyl cellulose was detected by the above method, and the detection data are shown in Table 3. The recovery rate was calculated according to the measured data.

[0037] Table 3:

[0038]

[0039] The pretreatment step of the HPLC-CAD method provided by the present invention is simple. It can not only detect the content of hydroxypropyl cellulose, but also reflect the type differences. As can be seen from Table 3, the detection results of the detection method provided by the present invention have high accuracy and precision, and have repeatability.

[0040] The preferred embodiments of the present invention disclosed above are only used to help explain the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific embodiments described. Obviously, many modifications and variations can be made according to the content of this specification. These embodiments are selected and specifically described in this specification to better explain the principle and practical application of the present invention, so that those skilled in the art can understand and utilize the present invention well. The present invention is only limited by the claims and their full scope and equivalents.

Claims

1. A method for determining the content of hydroxypropyl cellulose, characterized in that, it comprises the following steps: S1. Weigh high-substituted hydroxypropyl cellulose, use water or a polar organic solvent as a solvent to prepare a hydroxypropyl cellulose solution, and after dilution, obtain a series of hydroxypropyl cellulose reference solutions with different concentrations; S2. Take a preparation sample of the excipient containing the high-substituted hydroxypropyl cellulose described in step S1, grind it, weigh the fine powder, extract it in a water bath and prepare a corresponding test solution; S3. Use the HPLC-CAD method to detect the series of hydroxypropyl cellulose reference solutions obtained in step S1, obtain the peak area of hydroxypropyl cellulose in the reference solution, and draw a standard curve of the reference solution; S4. Use the HPLC-CAD method to determine the test solution with the target concentration and obtain the target peak information, and then use the external standard curve method to calculate the content of hydroxypropyl cellulose in the test solution; In the above steps, the HPLC-CAD method uses a chromatographic column filled with octadecylsilane-bonded silica gel; Among them, the parameters of the HPLC-CAD method are specifically: use acetonitrile or a methanol-water system as the mobile phase for gradient elution, use a Presto FF-C18 chromatographic column as the chromatographic column, use CAD as the detector, the column temperature is 40-80°C, the flow rate is 0.3-0.8 mL / min, and the specific gradient program is: 。 2. A method for determining the content of hydroxypropyl cellulose according to claim 1, characterized in that, in step S1, the content of the hydroxypropyl cellulose solution before dilution is 5 wt%.

3. A method for determining the content of hydroxypropyl cellulose according to claim 2, characterized in that, in step S1, the concentrations of the series of hydroxypropyl cellulose reference solutions are 3.775 μg / mL, 15.1 μg / mL, 37.75 μg / mL, 75.5 μg / mL, 113.25 μg / mL, and 151 μg / mL respectively.

4. A method for determining the content of hydroxypropyl cellulose according to any one of claims 1-3, characterized in that, the polar organic solvent includes at least one of acetonitrile, methanol, ethanol, and isopropanol.

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