CN-122017076-A - Method for detecting carbomer content in pharmaceutical preparation

Abstract

The invention relates to a detection method of carbomer content in a pharmaceutical preparation, which is used for solving the problems of high detection cost and auxiliary material interference in the prior art. The invention adopts urea and guanidine organic alkali added in sample pretreatment to weaken the influence of preparation auxiliary materials on carbomer neutralization reaction, adopts excessive berberine to fully combine with carboxylic acid groups in carbomer, then detects the residual concentration of berberine, establishes the linear relation of carbomer and berberine reaction, and calculates the carbomer content in the sample. The detection method established by the invention is applicable to different preparation formulas, the detection means is more flexible, and the method is suitable for industrialized popularization.

Inventors

• YANG HAIQING
• WANG FANGFANG
• ZHANG HAN
• ZHAO HONGSHU
• ZHU LINNA
• Li Miankui
• LI WENDONG
• LIU DANFENG

Assignees

• 浙江康恩贝制药股份有限公司

Dates

Publication Date

20260512

Application Date

20260312

Claims (10)

1. 1. A method for detecting the carbomer content of a pharmaceutical formulation, comprising the steps of: (1) Preparing a blank test sample, namely adding a carbomer-free pharmaceutical preparation into 2-8 times of urea or guanidine organic alkali solution, heating for dissolving, centrifuging, and taking a lower layer solution as the blank test sample solution; (2) Preparing a linear sample, namely adding a carbomer solution into a blank sample solution, adding berberine, standing, centrifuging, and taking supernatant to obtain the linear sample solution, wherein the dosage ratio of the berberine to the carbomer is not less than 18:1; (3) Drawing a standard curve, namely detecting the berberine content of the linear sample solution, determining the berberine consumption of the linear sample by comparing the berberine addition in the step (2), and establishing a standard curve of the carbomer content and the berberine consumption; (4) The test sample is determined by processing the pharmaceutical preparation to be tested according to the method of the step (1), adding berberine, centrifuging to obtain supernatant, wherein the dosage of the berberine is more than 18 times of the carbomer content in the pharmaceutical preparation to be tested, detecting the content of the berberine, and calculating the carbomer content by adopting the standard curve of the step (3).
2. 2. The method according to claim 1, wherein the amount of urea or guanidine organic base used in the step (1) is 4 times the amount of the pharmaceutical preparation.
3. 3. The detection method according to claim 1 or 2, wherein the guanidine organic base is one or more selected from guanidine hydrochloride, guanidine sulfate, guanidine carbonate, guanidine nitrate, and guanidine phosphate.
4. 4. The detection method according to claim 1, wherein the ratio of berberine to carbomer in the step (2) is 18-42:1, and the standing time is 10-20 min.
5. 5. The method according to claim 4, wherein the ratio of berberine to carbomer is 20:1.
6. 6. The detection method according to claim 1, wherein the heating in the step (1) is water bath heating for 10-20 min, and the centrifugal speed is 10000 rpm~14000 rpm.
7. 7. The method according to claim 1, wherein the berberine content detection method is selected from one of high performance liquid chromatography, ultra-high performance liquid chromatography, ultraviolet-visible spectrophotometry, and fluorescence spectrometry.
8. 8. The method according to claim 7, wherein the chromatographic column of the high performance liquid chromatography is an octadecylsilane chemically bonded silica packed column, mobile phase A is a 0.4% triethylamine solution with pH of 4.5, and mobile phase B is acetonitrile or methanol.
9. 9. The method according to claim 7, wherein the high performance liquid chromatography or ultra-high performance liquid chromatography calculates the berberine content in the samples of steps (3) and (4) by berberine reference substance concentration and peak area.
10. 10. The method according to claim 7, wherein the berberine content detection method is ultraviolet-visible spectrophotometry, calculating the berberine content in the samples in the steps (3) and (4) through the berberine reference substance concentration and the absorbance.

Description

Method for detecting carbomer content in pharmaceutical preparation Technical Field The invention belongs to the technical field of analytical chemistry, and particularly relates to a detection method for carbomer content in a pharmaceutical preparation. Background Carbomers are high molecular polymers formed by crosslinking a polyalkyl sucrose or a polyalkyl pentaerythritol with acrylic acid, wherein different materials and different degrees of polymerization combine to form products of different properties and efficacy. The carbomer has strong moisture absorption capability and strong static electricity, and the carbomer is acidic because the carbomer contains 52% -68% of carboxylic acid groups in the internal structure. The carbomer is curled before contact with water, and when the powder is fused with water, the curled molecular chain is slowly released, and alkali matter may be used to neutralize the carbomer in water dispersion with pH of 2.5-3.0, and the carboxyl of the carbomer is ionized to form gel. Carbomers have good cohesiveness, emulsifying property, solubility, thickening property, suspending property and film forming property, no allergic reaction, and stable and safe drug effect. The preparation has good compressibility under low pressure, high availability and strong in vivo and in vitro correlation, and can be used for preparation types such as gel, semisolid preparation, solid preparation, bioadhesive and the like. The existing carbomer content detection method comprises the steps of acid-base titration, drying weighing, high performance liquid chromatography and the like. CN117630230A (method for measuring carbomer content in preparation by high performance liquid chromatography evaporative light scattering method) (application day: 2023.12.21; publication day: 2024.03.01) discloses the chromatographic conditions of carbomer HPLC-ELSD method, wherein octadecylsilane chemically bonded silica column is used as chromatographic column, water or 0.02% formic acid aqueous solution is used as mobile phase A, acetone is used as mobile phase B, ethanol is used as mobile phase C, gradient elution is carried out, the temperature of drift tube of evaporative light scattering detector is 45-65 ℃, and the flow rate of nitrogen is 1.8-3.0L/min. According to the technical scheme, a standard curve is established by utilizing the linear relation between the logarithm of the peak area of carbomer in the evaporative light scattering detector and the logarithm of the concentration, so that quantitative detection is realized. However, the method has higher requirements on detection equipment and high detection cost. CN120293753A (application day: 2025.01.13; publication day: 2025.07.11) discloses that the eye drops are washed and centrifuged twice to separate carbomer, brinzolamide and other auxiliary materials in the eye drops, and the carbomer and brinzolamide are obtained by adopting a drying and weighing mode, and the brinzolamide weight is subtracted to obtain the carbomer content in the sample. The water-washing centrifugation step of the method cannot exclude interference of other polymer auxiliary materials on detection of carbomer content. The acid-base titration method is mainly implemented by reacting a strong base with carboxylic acid groups in carbomers. CN115015143A (application date: 2022.08.08; publication date: 2022.09.06) is a method for analyzing carbomer homopolymer in a transdermal absorption preparation, wherein sodium hydroxide is adopted to dissociate free carboxyl groups of the carbomer homopolymer into carboxylate ions, a complex is generated by combining calcium ions and the carboxylate ions, carbomer is extracted and separated, uncomplexed calcium is detected by adopting a flame atomic absorption spectrophotometry, and the content of the carbomer homopolymer is calculated by the content of the complexed calcium. The method has the advantages of very common detection instrument, high price, high detection cost, sample pretreatment time of more than 2 hours and long detection time. CN112461826A (method for measuring carbomer content in gel containing carbomer) (application day: 2017.06.29; publication day: 2021.03.09) adopts strong alkali solution to make carboxylic acid group of carbomer in gel exist in ion state, then adds excessive metal salt solution to make metal salt fully combine with carboxylic acid group in carbomer to form complex, after removing complex, then uses coordination titration to drop unbound metal salt so as to calculate carbomer content in sample. The back titration method has the defects that the detection result is interfered by the metal ion bulk drug or auxiliary materials (such as EDTA) in the preparation formula, and the sample pretreatment time of the method is longer than 2 hours, so that the detection time is long. Disclosure of Invention The invention aims to provide a method for detecting carbomer content in a pharmaceutical preparation, which is us