阅读说明：本技术 一种微晶纤维素-羧甲基纤维素钠的含量测定方法 (Content determination method of microcrystalline cellulose-sodium carboxymethylcellulose ) 是由 陈亚洲 秦松萍 张瑜 于 2020-12-24 设计创作，主要内容包括：本发明涉及一种微晶纤维素-羧甲基纤维素钠的含量测定方法,所述的方法为采用滴定法测定微晶纤维素-羧甲基纤维素钠中羧甲基纤维素钠的含量：取微晶纤维素-羧甲基纤维素钠2000mg,置250mL具有玻璃塞的锥形瓶中,加75mL冰醋酸,连接冷凝管,回流1.8-2.2小时,放冷,转移混合物至250mL烧杯中,并用少量冰醋酸润洗；用浓度为0.1N的高氯酸二氧六环溶液直接滴定；用电位判断滴定终点。该方法操作简便、专属性强、灵敏度高、重复性好。(The invention relates to a method for measuring the content of microcrystalline cellulose-sodium carboxymethylcellulose, which comprises the following steps of measuring the content of sodium carboxymethylcellulose in the microcrystalline cellulose-sodium carboxymethylcellulose by adopting a titration method: placing 2000mg of microcrystalline cellulose-sodium carboxymethylcellulose in a 250mL conical flask with a glass plug, adding 75mL of glacial acetic acid, connecting a condensation tube, refluxing for 1.8-2.2 hours, cooling, transferring the mixture to a 250mL beaker, and rinsing with a small amount of glacial acetic acid; directly titrating by using a perchloric acid dioxane solution with the concentration of 0.1N; the titration end point is judged by the electric potential. The method has the advantages of simple operation, strong specificity, high sensitivity and good repeatability.)

1. The content determination method of the microcrystalline cellulose-sodium carboxymethylcellulose is characterized by comprising a titration method.

2. The method for determining the content of the microcrystalline cellulose-sodium carboxymethyl cellulose according to claim 1, wherein the method is to determine the content of the sodium carboxymethyl cellulose in the microcrystalline cellulose-sodium carboxymethyl cellulose.

3. The method for determining the content of microcrystalline cellulose-sodium carboxymethylcellulose according to claim 2, which is characterized by comprising the following steps:

preparation of a test solution: placing 2000mg of microcrystalline cellulose-sodium carboxymethylcellulose in a 250mL conical flask with a glass plug, adding 75mL of glacial acetic acid, connecting a condensation tube, refluxing for 1.8-2.2 hours, cooling, transferring the mixture to a 250mL beaker, and rinsing with a small amount of glacial acetic acid;

directly titrating by using a perchloric acid dioxane solution with the concentration of 0.1N; judging a titration end point by using a potential;

calculating the content of the sodium methylcellulose according to the following formula: result = [ (Vs × N × F)/W ] × 100; wherein Vs is the volume of the sample consumed titration solution, mL; n is the concentration of the titration solution, mEq/mL; f is the titer, 296.0 mg/mEq; w is the weight of the sample, mg.

4. The method for measuring the content of microcrystalline cellulose-sodium carboxymethylcellulose according to claim 3, wherein the method for determining the titration endpoint by using the potential comprises the following steps:

placing a beaker filled with a test solution on an electromagnetic stirrer, immersing an electrode, stirring, and dropwise adding a titration solution from a burette in times; adding more amount at the beginning, stirring, and recording potential; and drawing a titration curve by taking the potential (E) of the indicating electrode as a vertical coordinate and the volume (V) of the titration solution as a horizontal coordinate, and taking the midpoint of the steep rising or falling part of the titration curve or the inflection point of the titration curve as a titration endpoint.

5. The method for determining the content of microcrystalline cellulose-sodium carboxymethylcellulose according to claim 4, wherein the time for refluxing is 2 hours.

Technical Field

The invention relates to a high polymer material composition, in particular to a detection method of the high polymer material composition.

Background

Microcrystalline cellulose (MCC) is a straight-chain polysaccharide substance combined by beta-1, 4-glucoside bonds as a main component, and is white, odorless and tasteless crystalline powder which is formed by superfine, short rod-shaped or powdery porous particles capable of freely flowing and hydrolyzed to the limit degree of polymerization (LOOP) by dilute acid of natural cellulose.

The microcrystalline cellulose has a particle size of 20-80 μm, a limiting degree of polymerization (LODP) of 15-375, and is nonfibrous and extremely fluid. The water insoluble, dilute acid, organic solvent and grease are partially dissolved and swelled in dilute alkali solution, and have high reaction performance in the carboxymethylation, acetylation and esterification processes. Because of the special properties of low polymerization degree, large specific surface area and the like, the microcrystalline cellulose is widely applied to the industries of medicine, food, cosmetics and the like.

In the pharmaceutical industry, microcrystalline cellulose is commonly used as an adsorbent, suspending agent, diluent, disintegrant. Microcrystalline cellulose is widely used in pharmaceutical formulations, mainly as diluent and binder in oral tablets and capsules, not only for wet granulation but also for dry direct compression. Also has certain lubricating and disintegrating effects, and is very useful in the preparation of tablets. The microcrystalline cellulose powder can form stable dispersion system in water, and can be mixed with medicine to make into cream-like or suspension-like medicinal liquid, and can also be used as capsule. Microcrystalline cellulose is vigorously stirred in water to form a gel, which can also be used to make paste and suspension type pharmaceutical preparations.

Sodium carboxymethylcellulose is an organic substance having the chemical formula [ C ]₆H₇O₂（OH）₂OCH₂COONa]n, is a carboxymethylated derivative of cellulose, the most predominant ionic cellulose gum. Sodium carboxymethylcellulose is an anionic polymer compound usually prepared by reacting natural cellulose with caustic alkali and monochloroacetic acid, and has a molecular weight of several thousands to millions. CMC-Na is white fibrous or granular powder, has no odor, and hygroscopicity, and can be easily dispersed in water to form transparent colloidal solution.

Microcrystalline Cellulose-Sodium Carboxymethylcellulose (Microcrystalline Cellulose and carboxymethyl Cellulose Sodium) is a premix of Microcrystalline Cellulose and carboxymethyl Cellulose, a white or off-white tasteless powder, has strong hygroscopicity, and contains 5-22% Sodium Carboxymethylcellulose. It is a water dispersible organic hydrocolloid.

The emergence of microcrystalline cellulose-sodium carboxymethylcellulose was dependent on the development of the technology for maximum colloidal dispersion in water. As a pharmaceutical adjuvant, it can be used as a carrier for making a dispersion highly thixotropic, a large amount of colloidal microcrystals are completely dispersed in particles produced in an aqueous medium, a network is established to prevent sedimentation of drug particles, and such a gel structure is easily broken by gentle shaking, thereby easily producing a pourable liquid. After removal of the shear force, the gel structure will re-establish. Thus, microcrystalline cellulose-sodium carboxymethylcellulose can act as a stable suspension medium to prevent phase separation.

Because of the ultimate application to the human body, there are severe requirements in the art for controlling the quality of pharmaceutical materials, including controlling the quality of pharmaceutical excipients. As mentioned above, the microcrystalline cellulose-sodium carboxymethylcellulose is used as a common pharmaceutical adjuvant, and the detection of the content of the active ingredients has important significance for controlling the quality of the active ingredients. In the prior art (such as the four parts of the 2020 edition of Chinese pharmacopoeia), a specific method is not disclosed, so how to measure the content of the microcrystalline cellulose-sodium carboxymethylcellulose is a technical problem to be solved urgently.

Disclosure of Invention

The invention aims to solve the technical problem of providing a content determination method of microcrystalline cellulose-sodium carboxymethylcellulose, which is simple and convenient to operate, strong in specificity, high in sensitivity and good in repeatability, and can be used for detecting the quality of the microcrystalline cellulose-sodium carboxymethylcellulose.

In order to solve the technical problems, the invention adopts the following technical scheme:

the method is a titration method.

The method is to determine the content of the sodium carboxymethyl cellulose in the microcrystalline cellulose-sodium carboxymethyl cellulose.

Preferably, the method specifically operates as follows:

preparation of a test solution: placing 2000mg of microcrystalline cellulose-sodium carboxymethylcellulose in a 250mL conical flask with a glass plug, adding 75mL of glacial acetic acid, connecting a condensation tube, refluxing for 1.8-2.2 hours, cooling, transferring the mixture to a 250mL beaker, and rinsing with a small amount of glacial acetic acid;

directly titrating by using a perchloric acid dioxane solution with the concentration of 0.1N; judging a titration end point by using a potential;

calculating the content of the sodium methylcellulose according to the following formula: result = [ (Vs × N × F)/W ] × 100; wherein Vs is the volume of the sample consumed titration solution, mL; n is the concentration of the titration solution, mEq/mL; f is the titer, 296.0 mg/mEq; w is the weight of the sample, mg.

Preferably, the method for judging the titration endpoint by using the electric potential comprises the following steps:

placing a beaker filled with a test solution on an electromagnetic stirrer, immersing an electrode, stirring, and dropwise adding a titration solution from a burette in times; adding more amount at the beginning, stirring, and recording potential; and drawing a titration curve by taking the potential (E) of the indicating electrode as a vertical coordinate and the volume (V) of the titration solution as a horizontal coordinate, and taking the midpoint of the steep rising or falling part of the titration curve or the inflection point of the titration curve as a titration endpoint.

Preferably, the time of the reflux is 2 hours.

The beneficial effects of the invention are mainly embodied in the following aspects:

1. the method of the invention has simple operation and low requirements on instruments.

2. The method has strong specificity.

3. The method has good repeatability.

4. The method has high sensitivity.

The technical effect of the method of the present invention can be demonstrated by the following tests.

Test examples methodological verification

1. Specificity

Taking microcrystalline cellulose, preparing a test solution according to the method, and titrating until a titration end point does not appear. The result shows that the microcrystalline cellulose has no obvious interference on the measurement result.

2. Repeatability of

The content of the sodium carboxymethyl cellulose in the same batch of microcrystalline cellulose-sodium carboxymethyl cellulose is continuously measured by the method, the result is shown in table 1, and the result shows that the method has good repeatability.

TABLE 1 repeatability of the method of the invention

Number of times	1	2	3	4	5	6	Av	RSD
									Results (% of indicated amount)	100.10	100.03	100.32	99.87	100.94	99.82	100.20	0.41

3. Intermediate precision

The same batch of microcrystalline cellulose-sodium carboxymethylcellulose is taken and measured by two different testers at different times, and the results are shown in table 2, which shows that the method has good intermediate precision.

TABLE 2 intermediate precision of the process of the invention

Detailed Description

The examples are for illustrative purposes only and are not to be construed as limiting the present patent.

EXAMPLE 1 determination of the content of sodium carboxymethylcellulose in microcrystalline cellulose-sodium carboxymethylcellulose

Preparation of a test solution: placing 2000mg of microcrystalline cellulose-sodium carboxymethylcellulose in a 250mL conical flask with a glass plug, adding 75mL of glacial acetic acid, connecting a condensation tube, refluxing for 1.8 hours, cooling, transferring the mixture to a 250mL beaker, and rinsing with a small amount of glacial acetic acid;

directly titrating by using a perchloric acid dioxane solution with the concentration of 0.1N; judging a titration end point by using a potential;

calculating the content of the sodium methylcellulose according to the following formula: result = [ (Vs × N × F)/W ] × 100; wherein Vs is the volume of the sample consumed titration solution, mL; n is the concentration of the titration solution, mEq/mL; f is the titer, 296.0 mg/mEq; w is the weight of the sample, mg.

The method for judging the titration endpoint by using the electric potential comprises the following steps:

placing a beaker filled with a test solution on an electromagnetic stirrer, immersing an electrode, stirring, and dropwise adding a titration solution from a burette in times; adding more amount at the beginning, stirring, and recording potential; and drawing a titration curve by taking the potential (E) of the indicating electrode as a vertical coordinate and the volume (V) of the titration solution as a horizontal coordinate, and taking the midpoint of the steep rising or falling part of the titration curve or the inflection point of the titration curve as a titration endpoint.

EXAMPLE 2 determination of the content of sodium carboxymethylcellulose in microcrystalline cellulose-sodium carboxymethylcellulose

Preparation of a test solution: placing 2000mg of microcrystalline cellulose-sodium carboxymethylcellulose in a 250mL conical flask with a glass plug, adding 75mL of glacial acetic acid, connecting a condensation tube, refluxing for 2.2 hours, cooling, transferring the mixture to a 250mL beaker, and rinsing with a small amount of glacial acetic acid;

directly titrating by using a perchloric acid dioxane solution with the concentration of 0.1N; judging a titration end point by using a potential;

calculating the content of the sodium methylcellulose according to the following formula: result = [ (Vs × N × F)/W ] × 100; wherein Vs is the volume of the sample consumed titration solution, mL; n is the concentration of the titration solution, mEq/mL; f is the titer, 296.0 mg/mEq; w is the weight of the sample, mg.

The method for judging the titration endpoint by using the electric potential comprises the following steps:

placing a beaker filled with a test solution on an electromagnetic stirrer, immersing an electrode, stirring, and dropwise adding a titration solution from a burette in times; adding more amount at the beginning, stirring, and recording potential; and drawing a titration curve by taking the potential (E) of the indicating electrode as a vertical coordinate and the volume (V) of the titration solution as a horizontal coordinate, and taking the midpoint of the steep rising or falling part of the titration curve or the inflection point of the titration curve as a titration endpoint.

EXAMPLE 3 determination of the content of sodium carboxymethylcellulose in microcrystalline cellulose-sodium carboxymethylcellulose

Preparation of a test solution: placing 2000mg of microcrystalline cellulose-sodium carboxymethylcellulose in a 250mL conical flask with a glass plug, adding 75mL of glacial acetic acid, connecting a condensation tube, refluxing for 2 hours, cooling, transferring the mixture to a 250mL beaker, and rinsing with a small amount of glacial acetic acid;

directly titrating by using a perchloric acid dioxane solution with the concentration of 0.1N; judging a titration end point by using a potential;

calculating the content of the sodium methylcellulose according to the following formula: result = [ (Vs × N × F)/W ] × 100; wherein Vs is the volume of the sample consumed titration solution, mL; n is the concentration of the titration solution, mEq/mL; f is the titer, 296.0 mg/mEq; w is the weight of the sample, mg.

The method for judging the titration endpoint by using the electric potential comprises the following steps:

placing a beaker filled with a test solution on an electromagnetic stirrer, immersing an electrode, stirring, and dropwise adding a titration solution from a burette in times; adding more amount at the beginning, stirring, and recording potential; and drawing a titration curve by taking the potential (E) of the indicating electrode as a vertical coordinate and the volume (V) of the titration solution as a horizontal coordinate, and taking the midpoint of the steep rising or falling part of the titration curve or the inflection point of the titration curve as a titration endpoint.

It should be understood that the above examples are only for clearly illustrating the technical solutions and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.