Method for determining content of sodium carboxymethyl cellulose in gel

Abstract

The invention discloses a method for measuring the content of sodium carboxymethyl cellulose in a gel. The method comprises the following steps: (1) precisely weighing a medicinal gel containing sodium carboxymethyl cellulose, and putting the medicinal gel into a conical flask; (2) adding ethanol, fully shaking, and then carrying out ultrasonic treatment; (3) standing under a refrigeration condition or a room temperature condition, and filtering by a G4 vertical melting funnel with constant weight at 105 DEG C; (4) adding ethanol into the conical flask, filtering the washing liquid in the same G4 vertical melting funnel, and washing the filter residue; and (5) drying the G4 vertical melting funnel at 105 DEG C until the weight is constant, recording the difference between the constant weights of the G4 vertical melting funnel twice as the weight of the sodium carboxymethyl cellulose, and calculating the content of the sodium carboxymethyl cellulose. The determination method provided by the invention is simple and convenient to operate, has relatively low requirements on experimental equipment and technical level of testers, does not need to use a reference substance or a standard substance, and is low in cost.

Description

Technical Field

[0001] The invention relates to a method for determining the content of sodium carboxymethyl cellulose in a gelling agent, belonging to the technical field of drug analysis. Background Art

[0002] Sodium carboxymethyl cellulose, the structure is It is a type of sodium carboxymethyl cellulose salt generated by the reaction of cellulose with sodium monochloroacetate under alkaline conditions. Due to its wide source and unique physical properties, it has outstanding applications in food, medicine, polymer materials and other fields.

[0003] Sodium carboxymethyl cellulose is a common pharmaceutical excipient, often used as a coating material, disintegrant, thickener, adhesive, etc. In the research process of generic drugs, it is necessary to reversely analyze the types and contents of pharmaceutical excipients in the prescription through the reference preparation, so as to imitate the generic drug with the same indicators as the reference preparation as possible.

[0004] Sodium carboxymethyl cellulose is a common matrix component of gel drugs. The dosage can affect the viscosity, rheological properties and other properties of the gel drugs, further affecting the release of active ingredients in the gel drugs, irritation to the body, etc. Therefore, a method that can reversely analyze the content of sodium carboxymethyl cellulose in gel drugs is urgently needed.

[0005] At present, the methods for detecting the content of sodium carboxymethyl cellulose are mostly gel chromatography, iodine titration and colorimetry, but these methods are cumbersome to operate and have high requirements for equipment and reference materials, and cannot simply, conveniently and cost-effectively determine the content of sodium carboxymethyl cellulose in gel drugs. Summary of the invention

[0006] In view of at least one problem existing in the above-mentioned prior art, the present invention provides a method for determining the content of sodium carboxymethyl cellulose in a gel, which adopts a gravimetric analysis method and relies on the different solubility properties of raw and auxiliary materials in the gel drug to separate and determine the content of sodium carboxymethyl cellulose; the determination method of the present invention is simple and convenient to operate, and has relatively low requirements on experimental equipment and the technical level of experimental personnel, and does not require the use of reference substances or standard substances, and has low cost.

[0007] In order to achieve the above object, the present invention adopts the following technical scheme: a method for determining the content of sodium carboxymethyl cellulose in a gel, comprising the following steps: (1) Accurately weigh 0.5-2.0 g of the drug gel containing sodium carboxymethyl cellulose, recorded as W. 供 , placed in a conical flask; (2) Add 30-70 ml of ethanol to the drug gel prepared in step (1), shake thoroughly, and then perform ultrasonic treatment; (3) Dry the clean G4 fritted funnel at 105°C to constant weight and set aside. The G4 fritted funnel with constant weight is recorded as W1. Place the ethanol solution of the drug gel in step (2) under refrigeration or room temperature and let it stand for 0.5 to 2 hours. Then transfer all the contents in the conical flask to the prepared G4 fritted funnel for filtration. (4) Rinse the conical flask in step (3) with 50 ml of ethanol three times, combine the washings and filter them in the same G4 vertical fritted funnel, and finally rinse the filter residue with 20-100 ml of ethanol; (5) Dry the G4 fused funnel containing the filter residue at 105°C until it reaches a constant weight. The constant weight of the G4 fused funnel is recorded as W2. The weight difference between W2 and W1 is the weight of sodium carboxymethyl cellulose. The calculation formula is: (W2-W1) / W 供 ×100%, to obtain the content of sodium carboxymethyl cellulose in the gel drug.

[0008] Preferably, in step (1), the drug gel is lidocaine hydrochloride gel.

[0009] Preferably, in step (1), the content of sodium carboxymethyl cellulose in the pharmaceutical gel is 1.0-10.0%.

[0010] Preferably, in step (1), the content of sodium carboxymethyl cellulose in the pharmaceutical gel is 3.5%.

[0011] Preferably, in step (1), the detection amount of the drug gel is 1 g.

[0012] Preferably, in step (2), the amount of ethanol used is 50 ml.

[0013] Preferably, in step (2), the ultrasonication time is 5 to 15 minutes.

[0014] Preferably, in step (2), the ultrasonic time is 10 min.

[0015] Preferably, in step (3), the refrigeration condition is 2-8°C.

[0016] Preferably, in step (3), the room temperature is 20-25°C.

[0017] Preferably, in step (3), the mixture is allowed to stand for 1 hour.

[0018] Preferably, in step (4), the amount of ethanol used for washing the filter residue is 50 ml.

[0019] Compared with the prior art, the invention has the following beneficial effects: the method for determining the content of sodium carboxymethyl cellulose in a gel is a gravimetric method, which relies on the different solubility properties of raw and auxiliary materials in a gel drug to separate and determine the content of sodium carboxymethyl cellulose; the determination method of the invention uses only one reagent, ethanol, and only two devices, an oven and an electronic balance, so the detection cost is low; in the determination method of the invention, the three steps of precipitation, filtration and drying are carried out, so the operation is simple and the time consumption is short; the method for determining the content of sodium carboxymethyl cellulose in a gel has relatively low requirements on experimental equipment and the technical level of experimental personnel. DETAILED DESCRIPTION

[0020] The following is a clear and complete description of the technical solutions in the implementation of the present invention. 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 ordinary technicians in the field without making creative work are within the scope of protection of the present invention. If the specific conditions are not specified in the embodiments, they are carried out according to the normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents, instruments, and components used, they are all conventional products that can be purchased commercially.

[0021] Example 1 A method for determining the content of sodium carboxymethyl cellulose in a gel, the specific determination steps are as follows: (1) Accurately weigh 1 g of lidocaine hydrochloride gel with a sodium carboxymethylcellulose content of 3.5%, record it as W 供 , placed in a conical flask; (2) Add 50 ml of ethanol to the lidocaine hydrochloride gel of step (1), shake thoroughly, and then perform ultrasonic treatment at an ultrasonic power of 500 W for 10 min; (3) Dry the clean G4 fritted funnel at 105°C to constant weight and set aside. The G4 fritted funnel with constant weight is recorded as W1. Place the ethanol solution of lidocaine hydrochloride gel in step (2) at room temperature of 20-25°C and let it stand for 1 hour. Then transfer all the contents in the conical flask to the prepared G4 fritted funnel for filtration. (4) Rinse the conical flask in step (3) with 50 ml of ethanol three times, combine the washings and filter them in the same G4 vertical fritted funnel, and finally rinse the filter residue with 50 ml of ethanol; (5) Dry the G4 fused funnel containing the filter residue at 105°C until it reaches a constant weight. The constant weight of the G4 fused funnel is recorded as W2. The weight difference between W2 and W1 is the weight of sodium carboxymethyl cellulose. The calculation formula is: (W2-W1) / W 供 ×100%, to obtain the content of sodium carboxymethyl cellulose in the gel drug.

[0022] In this example, lidocaine hydrochloride gel is used as the drug gel, which is sourced from Sandoz Pharmaceuticals Co., Ltd., with a specification of 2% (30 ml: 0.6 g) and a batch number of 42620.

[0023] This example is one of the most representative implementation methods of the method of the present invention. Therefore, based on Example 1, the methodological validation was performed with reference to the 2020 edition of the Chinese Pharmacopoeia 9101 Analytical Method Validation Guidelines. The validation contents are as follows: Example 2 Specificity Test About 1.0 g of water, lidocaine hydrochloride, methylparaben, propylparaben, and sodium carboxymethylcellulose were weighed accurately, and the results were measured according to the method in Example 1. The data are shown in Table 1.

[0024] Among them: the source of the water used is purified water prepared in the pure water room of Yaoda Pharmaceutical Co., Ltd.; the source of the lidocaine hydrochloride used is Shandong Chenghui Shuangda Pharmaceutical Co., Ltd., with batch number 018210501; the source of the methylparaben used is Jiangxi Alpha Hi-Tech Pharmaceutical Co., Ltd., pharmaceutical excipient grade, batch number 20220801; the source of the propylparaben used is Shanghai Aladdin Biochemical Technology Co., Ltd., chemically pure, batch number I2111243; the source of the sodium carboxymethyl cellulose used is Anhui Shanhe Pharmaceutical Excipients Co., Ltd., pharmaceutical excipient grade, model SH-SJJ-4000, batch number 211221.

[0025] In the subsequent verification of Examples 3 to 6, unless otherwise specified, the information of the reagents used is the same as that of Example 2.

[0026] Table 1 Specificity test

[0027] The results showed that the weight of the filter residue in the G4 vertical fritted funnel corresponding to water, lidocaine hydrochloride, methylparaben and propylparaben was almost zero (within the range of ±0.0003g); the weight of the filter residue in the G4 vertical fritted funnel corresponding to sodium carboxymethyl cellulose was basically consistent with the sample weight, and the specificity of this method was good.

[0028] Example 3 Repeatability Test Accurately weigh 1.0 g of lidocaine hydrochloride gel with a sodium carboxymethylcellulose content of about 3.5%, and weigh 6 portions. Perform parallel determination according to the method of Example 1. The data are shown in Table 2; Among them: the source of the lidocaine hydrochloride gel used is Sandoz Pharmaceutical Co., Ltd., the specification is 2% (30ml: 0.6g), and the batch number is 42620.

[0029] Table 2 Repeatability test

[0030] The results showed that the average content of sodium carboxymethyl cellulose detected in 6 portions of lidocaine hydrochloride gel was 3.55% and the RSD was 0.4%, which had good repeatability and met the verification requirements.

[0031] Example 4 Intermediate Precision Test Six batches of lidocaine hydrochloride gel were tested in parallel by different personnel at different times, referring to the repeatability test in Example 6. The results are shown in Table 3. Among them: the source of the lidocaine hydrochloride gel used is Sandoz Pharmaceutical Co., Ltd., the specification is 2% (30ml: 0.6g), and the batch number is 42620.

[0032] Table 3 Intermediate precision test

[0033] The results showed that in two repeatability tests, 6 portions of lidocaine hydrochloride gel were measured in parallel, and the average contents of sodium carboxymethyl cellulose were 3.55% and 3.53%, respectively, with RSDs of 0.4% and 0.3%, respectively; in the 6 portions of lidocaine hydrochloride gel measured in two repeatability tests, the relative deviation of the average content of sodium carboxymethyl cellulose was 0.2%.

[0034] In this intermediate precision test, different personnel measured 12 portions of lidocaine hydrochloride gel in parallel at different times, and the average content of sodium carboxymethyl cellulose was detected to be 3.54%, with an RSD of 0.4%. The intermediate precision was good and met the verification requirements.

[0035] Example 5 Accuracy Test Lidocaine hydrochloride gels with sodium carboxymethylcellulose contents of about 1.0%, 3.5%, and 10.0% were prepared respectively, and the determination was repeated three times in parallel according to the method of Example 1. The results are shown in Table 4; Among them, the composition of lidocaine hydrochloride gel with a sodium carboxymethylcellulose content of about 1.0% is: 50.0015g of water, 1.0168g of lidocaine hydrochloride, 0.0306g of methylparaben, 0.0159g of propylparaben, and 0.5428g of sodium carboxymethylcellulose; The composition of lidocaine hydrochloride gel with a sodium carboxymethylcellulose content of about 3.5% is: 50.0446 g of water, 1.0091 g of lidocaine hydrochloride, 0.0301 g of methylparaben, 0.0151 g of propylparaben, and 1.8805 g of sodium carboxymethylcellulose; The composition of lidocaine hydrochloride gel with a sodium carboxymethylcellulose content of about 10% is: 50.0202g of water, 1.0243g of lidocaine hydrochloride, 0.0299g of methylparaben, 0.0155g of propylparaben, and 5.8857g of sodium carboxymethylcellulose.

[0036] Table 4 Accuracy test

[0037] The results showed that the recovery of sodium carboxymethyl cellulose in lidocaine hydrochloride gel with sodium carboxymethyl cellulose content of about 1.0%, 3.5%, and 10.0% was in the range of 98.1%~101.1%, with an RSD of 1.1%, which was highly accurate and met the verification requirements.

[0038] Example 6 Durability Test 1. Based on the method provided in Example 1, the following are controlled separately: A. Controlling the dosage of lidocaine hydrochloride gel: In step (1), the weighed amounts of lidocaine hydrochloride gel are 0.5 g and 2.0 g; B. Controlling the amount of ethanol: In step (2), the amount of ethanol used is 30 ml and 70 ml; C. Controlling the ultrasonic time: In step (2), the ultrasonic time is 5 min and 15 min; E. Controlling ultrasonic power: In step (2), the ultrasonic power is 400 W and 600 W; F. Controlling the static environment: In step (3), the static environment is a refrigerated condition (2-8°C); In addition, the other determination conditions and operations were not changed, and the content of sodium carboxymethylcellulose in the same batch of lidocaine hydrochloride gel was determined respectively, and compared with the detection amount of the determination method provided in Example 1. The results are shown in Table 5; The lidocaine hydrochloride gel used was from Sandoz Pharmaceuticals Co., Ltd., with a specification of 2% (30 ml: 0.6 g) and a batch number of 42620. 2. Three different types of sodium carboxymethyl cellulose (a, b, c) were used to prepare lidocaine hydrochloride gel, and the method of Example 1 was used for three parallel measurements. The results are shown in Table 6. The source of the sodium carboxymethyl cellulose used is Anhui Shanhe Pharmaceutical Excipients Co., Ltd., pharmaceutical excipient grade, model a is SH-SJJ-4000, batch number is 211221; model b is SH-SJJ-1000, batch number is 220812; model c is SH-SJJ-8000, batch number is 220501; The composition of lidocaine hydrochloride gel prepared using three types of sodium carboxymethyl cellulose a, b, and c is as follows: Type A lidocaine hydrochloride gel: water 50.0446 g, lidocaine hydrochloride 1.0091 g, methylparaben 0.0301 g, propylparaben 0.0151 g, sodium carboxymethylcellulose 1.8805 g; Model b lidocaine hydrochloride gel: water 50.0164 g, lidocaine hydrochloride 1.0004 g, methylparaben 0.0302 g, propylparaben 0.0156 g, sodium carboxymethylcellulose 1.8692 g; Model A lidocaine hydrochloride gel: 50.0441 g water, 1.0033 g lidocaine hydrochloride, 0.0298 g methylparaben, 0.0153 g propylparaben, 1.9145 g sodium carboxymethylcellulose.

[0039] Table 5 Durability test (lidocaine hydrochloride gel of the same batch under different conditions)

[0040] Table 6 Durability test (different types of lidocaine hydrochloride gel under the same conditions)

[0041] Verification results: The content of sodium carboxymethyl cellulose in the same batch of lidocaine hydrochloride gel measured under various durability conditions was in the range of 3.50%~3.58%, and the ratio to the amount measured under standard conditions was in the range of 0.99~1.01; in lidocaine hydrochloride gel prepared with the same type of sodium carboxymethyl cellulose, the recovery rate of sodium carboxymethyl cellulose was detected in the range of 98.6%~101.4%, and the RSD was lower than 5.0%, with good durability and meeting the verification requirements.

[0042] Through the above examples, the method for determining the content of sodium carboxymethyl cellulose in the gel provided by the present invention has undergone complete methodological verification, and the verification results show that the method has high specificity, good repeatability, good intermediate precision, high accuracy, and good durability, and can be used as a conventional determination method to perform quality control on the content of sodium carboxymethyl cellulose in lidocaine hydrochloride gel.

[0043] Comparative Example 1 A method for determining the content of sodium carboxymethyl cellulose in a gel, wherein the specific determination steps are different from those in Example 1 in that: in step (2), the amount of ethanol used is 10 ml; The rest is exactly the same as in Example 1.

[0044] Comparative Example 2 A method for determining the content of sodium carboxymethyl cellulose in a gelling agent, which is different from Example 1 in that: ultrasonic treatment is not performed in step (2); The rest is exactly the same as in Example 1.

[0045] Comparative Example 3 A method for determining the content of sodium carboxymethyl cellulose in a gelling agent, which is different from Example 1 in that: in step (3) and step (4), the G4 vertical melting funnel is kept at a constant weight at 80°C; The rest is exactly the same as in Example 1.

[0046] Comparative Example 4 A method for determining the content of sodium carboxymethyl cellulose in a gelling agent, which is different from Example 1 in that: in step (3), ash-free filter paper with a constant weight at 105° C. is used for filtering in a glass funnel, and in step (4), the ash-free filter paper containing the filter residue is kept at a constant weight at 105° C. in a glass funnel; The rest is exactly the same as in Example 1.

[0047] The lidocaine hydrochloride gel used in the determination of the sodium carboxymethylcellulose content in Example 1 and Comparative Examples 1 to 4 was from the same batch and was summarized in the form of recovery rates as shown in Table 7.

[0048] Table 7 Recovery rate of Example 1 and Comparative Example 1 to Comparative Example 4

[0049] From Table 1 to Table 6, it can be found that the embodiments of the present invention are the most representative implementation methods, and the determination method of the present invention has passed a complete methodological verification, so the determination has high accuracy and good reproducibility.

[0050] As can be seen from Table 7, in Comparative Example 1, due to the low amount of ethanol used to precipitate sodium carboxymethyl cellulose, part of the sodium carboxymethyl cellulose was not precipitated, resulting in a decrease in the amount of filter residue in the funnel, and the final measured content result was low; since the amount of sodium carboxymethyl cellulose precipitated and the amount of ethanol were correlated within a certain range, the RSD was still within an acceptable range; in Comparative Example 2, since the precipitation step was not ultrasonicated, the precipitated sodium carboxymethyl cellulose was easily agglomerated and adsorbed on the bottle wall and could not be transferred to the funnel, resulting in a low measured content result, and due to the different adsorption conditions of each sample, the results were The RSD is on the high side; in Comparative Example 3, since the temperature for the final constant weight is low, it is not enough to completely volatilize the residual water or ethanol in the filter residue, resulting in a higher content result; since the three samples are all constant weight at 80°C, the residual water or ethanol levels should be similar, so the RSD is still within an acceptable range; in Comparative Example 4, due to the use of ash-free filter paper for filtration, there are trace components in the filter paper that can be washed away by the solvent, resulting in a decrease in the total weight of the filter paper and the filter residue after constant weight, making the measured content result low, and it is impossible to ensure that the flushing degree of each filter paper is consistent, so the RSD is on the high side.

[0051] In summary, the method provided by the present invention is a gravimetric analysis method, which relies on the different solubility properties of raw materials and auxiliary materials in gel drugs to separate and determine the content of sodium carboxymethyl cellulose. It is simple to operate through three steps of precipitation, filtration and drying, and only uses two devices, an oven and an electronic balance. The requirements for experimental equipment and the technical level of the test personnel are relatively low; at the same time, it avoids the use of reference substances or standard substances with different quality specifications on the market, which can not only reduce costs, but also significantly improve the parallelism and reproducibility of detection, and can meet the detection requirements of the content of sodium carboxymethyl cellulose in drug gels.

[0052] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit and essential features of the present invention. Therefore, the embodiments should be considered exemplary and non-restrictive in all respects, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims be included in the present invention.

[0053] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A method for determining the content of sodium carboxymethyl cellulose in a gelling agent, characterized in that: The following steps are involved: (1) Accurately weigh 0.5-2.0 g of the drug gel containing sodium carboxymethyl cellulose, denoted as W. 供 , placed in a conical flask; (2) adding 30-70 ml of ethanol to the drug gel prepared in step (1), shaking thoroughly, and then ultrasonically treating; (3) Dry the clean G4 fritted funnel at 105°C to constant weight and set it aside. The G4 fritted funnel with constant weight is recorded as W1. Place the ethanol solution of the drug gel in step (2) under refrigeration or room temperature and let it stand for 0.5 to 2 hours. Then, transfer all the materials in the conical flask to the prepared G4 fritted funnel for filtration. (4) Rinse the conical flask in step (3) with 50 ml of ethanol three times, combine the washings into the same G4 vertical fritted funnel for filtration, and finally rinse the filter residue with 20-100 ml of ethanol; (5) The G4 fused funnel containing the filter residue is dried at 105°C to a constant weight. The constant weight of the G4 fused funnel is recorded as W2. The weight difference between W2 and W1 is the weight of sodium carboxymethyl cellulose. The calculation formula is: (W2-W1) / W 供 × 100%, to obtain the content of sodium carboxymethyl cellulose in the gel drug.

2. The method for determining the content of sodium carboxymethyl cellulose in a gelling agent according to claim 1, characterized in that: In step (1), the drug gel is lidocaine hydrochloride gel.

3. A method for determining the content of sodium carboxymethylcellulose in a gelling agent according to claim 1 or 2, characterized in that: In step (1), the content of sodium carboxymethyl cellulose in the pharmaceutical gel is 1.0-10.0%.

4. The method for determining the content of sodium carboxymethyl cellulose in a gelling agent according to claim 3, characterized in that: In step (1), the content of sodium carboxymethyl cellulose in the pharmaceutical gel is 3.5%.

5. The method for determining the content of sodium carboxymethyl cellulose in a gelling agent according to claim 1, characterized in that: In step (1), the detection amount of the drug gel is 1 g.

6. The method for determining the content of sodium carboxymethyl cellulose in a gelling agent according to claim 1, characterized in that: In step (2), the amount of ethanol used is 50 ml.

7. The method for determining the content of sodium carboxymethylcellulose in a gelling agent according to claim 1, characterized in that: In step (2), the ultrasonic time is 5 to 15 minutes.

8. The method for determining the content of sodium carboxymethylcellulose in a gelling agent according to claim 1 or 7, characterized in that: In step (2), the ultrasonic time is 10 min.

9. The method for determining the content of sodium carboxymethylcellulose in a gel according to claim 1, characterized in that: In step (3), let stand for 1 h.

10. The method for determining the content of sodium carboxymethylcellulose in a gelling agent according to claim 1, characterized in that: In step (3), the refrigeration condition is 2-8°C; the room temperature condition is 20-25°C.

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