Shanghai Jiahang Instrument Co., LTD. : Chinese Pharmacopoeia relative density regulation and U type

I. Introduction

In the field of drug development, production and quality control, relative density is a key physical index, which plays an important role in evaluating the purity, quality stability and consistency of drugs. The implementation of the 2020 edition of "Chinese Pharmacopoeia" has brought new standards and methods for the determination of drug relative density, among which the new U-type oscillation densimeter method has injected new vitality for drug testing by virtue of its unique advantages. Shanghai Jiahang Instrument Co., Ltd. focuses on the development and manufacturing of instruments, closely follows the pace of pharmacopoeia, and deeply explores the application of U-type oscillation densimeter method in the determination of drug relative density, helping the pharmaceutical industry to improve the detection level.

Ii. Interpretation of the relative density determination provisions of the 2020 edition of Chinese Pharmacopoeia
(A) relative density definition and measurement significance

Relative density refers to the ratio of the density of a substance to the density of water under the same temperature and pressure conditions, usually specified as 20℃. The relative density of pure substance is constant under certain conditions, and the determination of the relative density of drug can effectively check the degree of pure impurity. Whether it is chemical raw materials, finished products, or traditional Chinese medicine, the relative density is closely related to the quality of drugs, and plays an indispensable role in controlling the load in the production process and determining the concentration of drugs in the research and development stage. There are many varieties involved in measuring relative density in Chinese Pharmacopoeia, including 238 traditional Chinese medicines and 50 chemical drugs, which highlights the important position of relative density measurement in drug quality control system.

(2) Review of traditional determination methods

The methods of pycnometer and Wechsler pycnometer included in the 2015 edition of Chinese Pharmacopoeia are the traditional methods of relative density determination. The specific gravity bottle method is suitable for general liquid drugs, and the relative density is calculated by precisely measuring the mass of a certain volume of samples and water. However, there are some problems such as difficult temperature control, tedious operation, long measurement time, large sample dosage and higher requirements for manual calculation and operation experience. Wechsler's gravity scale rule is used to determine the relative density of volatile liquid drugs, based on Archimedes' principle, through the readings in water and samples to calculate, but it also faces inconvenient operation and low efficiency.

(3) The principle of new U-type oscillation densitometer method

The U-type oscillation densitometer method belongs to the surface resonance method. Its principle is to place the sample in a U-shaped tube equipped with a counter. The U-shaped tube begins to oscillate under the excitation of electrons, and the oscillation frequency is related to the density of matter. The actual density of the substance is calculated by measuring the difference in frequency between the measured substance and the reference reference material (such as air and degassed water). The formula for density calculation of the method is ρ=A×T2−B, where A and B are instrumental constants, which can be determined by adding a known density of air and degassed water to the oscillator tube, and T is the oscillation period of the sample. This method has high measurement accuracy and has been included in international pharmacopoeia such as EP9.0/BP2017 (European Pharmacopoeia), JP16 (Japanese Pharmacopoeia) and USP40 (US Pharmacopoeia), and there are also relevant national standards in China (GB/T 29617-2013) for density and relative density testing of specific liquids.

Third, Shanghai Jiahang U-type oscillation densitometer product advantages
(1) Accurate measurement to meet the requirements of pharmacopoeia

The U-type oscillation densimeter of Shanghai Jiahang strictly follows the requirements of the 2020 edition of Chinese Pharmacopoeia for relative density measurement instruments, with reading accuracy of not less than ±0.001g/ml, and some high-precision products can reach ±0.0001g/ml. The instrument has built-in high-precision temperature sensor, with advanced temperature control system, the temperature can be accurately controlled at 20℃ or the temperature specified in the text of each variety, the temperature control accuracy can reach ±0.05℃, effectively reduce the impact of temperature on the measurement results, ensure the accuracy and reliability of the measurement data, and meet the strict requirements of the pharmacopeia for relative density measurement.

(2) Efficient and fast, improve the detection efficiency

Compared with the traditional measurement method, the Jiahang U-type oscillation densitometer greatly reduces the measurement time, only 3-5 minutes to complete a measurement, of which the temperature control can be completed in 1 minute. The sample amount is very small, only 2-3ml, which reduces the loss and waste of samples and improves the detection efficiency. The instrument is simple to operate, and the result directly displays the density/relative density, without tedious manual calculation, effectively avoiding calculation errors, and making the detection work more efficient and convenient.

(3) Complete functions to ensure measurement accuracy

Automatic calibration function: The instrument has an automatic calibration function, which can be calibrated periodically with substances of known density such as air and water to ensure the accuracy of the instrument constant. Users can also use standard substances to correct at different operating temperatures according to actual needs, and up to six groups of custom calibration can be carried out to further improve measurement accuracy.
Bubble detection and elimination: When measuring, the instrument can detect whether there is a bubble formation in the oscillating tube in real time. Once the bubble is found, it will remind the user to deal with it in time to avoid the interference of the bubble on the measurement result. At the same time, the instrument design helps to reduce the formation of bubbles and ensure the smooth progress of the measurement process.
Viscosity compensation function: For high viscosity samples, Jiahang U-type oscillation densitometer is equipped with viscosity compensation function. Recalibrate the instrument with built-in algorithm or select a density control substance with similar density and viscosity to the test product to effectively reduce the influence of viscosity on measurement accuracy and ensure accurate and reliable measurement results of high-viscosity samples.
(4) Data management, in accordance with regulatory requirements

The instrument has powerful data management function, can store 1000 sets of measurement data, and supports thermal printing and PC export. In addition, audit tracking software can also be selected to record key information during the operation of the instrument, such as measurement time, operator, calibration records, etc., in full compliance with FDA regulations, providing strong support for quality control and compliance management of drug manufacturers.

Four, U-type oscillation densitometer operation guide
(1) Boot preheating

After turning on the power supply, the instrument needs to be preheated and wait for the internal temperature to be balanced and stable. The preheating time depends on the instrument model and the ambient temperature, generally 10-15 minutes, to ensure that the instrument is in the best working condition to obtain accurate measurement results.

(2) Calibration verification

After each turn on, the instrument is calibrated using dry air and distilled water. Enter the standard density values of air and distilled water at the corresponding temperature and start the calibration procedure according to the prompts on the instrument operation interface. Once calibration is complete, it can be verified by measuring a standard sample of a known density to ensure that the instrument is measuring accurately. If the verification results exceed the allowable error range, the instrument needs to be recalibrated.

(III) Sample preparation and sampling

Pre-adjust the temperature of the test product to about 20 ° C or the temperature specified in the text of each variety to reduce the risk of bubbles in the U-shaped oscillation tube and shorten the measurement time.
Use a 2-3ml syringe to absorb the appropriate amount of sample and ensure that there are no bubbles in the sample. Slowly inject the sample into the U-shaped quartz glass tube to avoid sample splashing or bubble formation.
(4) Measurement and data processing

After the sample injection is completed, wait for the temperature of the sample to be measured to be equalized with the measured temperature. Select the appropriate measurement mode and start the measurement procedure. The instrument will automatically measure the oscillation period of the sample and calculate the density and relative density of the sample according to the built-in formula.
The measurement results are automatically saved and can be viewed directly on the instrument display. If you need to print or export data, follow the instrument operation guide. After the measurement is completed, the measurement data are recorded in time, and the data are analyzed and processed to determine whether the relative density of the drug meets the standards stipulated by the pharmacopoeia.
(5) Cleaning and maintenance

After each measurement, the U-shaped glass tube of the instrument must be thoroughly cleaned. Water soluble samples are washed repeatedly with water, then cleaned with alcohol, and finally dried with compressed air. The oil-soluble samples are cleaned with organic solvents such as acetone and petroleum ether according to the specific situation, then cleaned with alcohol, and finally dried with compressed air.
Regularly carry out comprehensive maintenance of the instrument, check whether the components of the instrument work normally, such as sensor accuracy, temperature control system performance, etc. If it is found that the instrument fails or the measurement error is large, it should be repaired and calibrated in time to ensure that the instrument is always in good working condition.
5. Application case sharing

The relative density of ethanol raw materials was measured by Shanghai Jiahang U-type oscillation densitometer in the chemical drug production workshop of a large pharmaceutical enterprise. In the past, the specific gravity bottle method was not only complicated in operation, but also greatly affected by the ambient temperature, and the measurement results fluctuated obviously. After switching to Jiahang U-type oscillation densitometer, the measurement time is shortened from the original several hours to less than 3 minutes, the measurement accuracy is significantly improved, and the data repeatability is good. By monitoring the relative density of ethanol raw material in real time, the quality of the raw material is effectively controlled, the product quality problems caused by raw material impurity are avoided, and the production efficiency and product quality stability are improved.

In the manufacturers of Chinese medicine preparations, the relative density detection of compound Chinese medicine oral liquid has always been the difficulty of quality control. Because of the complex composition of compound Chinese medicine, traditional methods are difficult to measure accurately. By optimizing the measurement parameters and adopting the viscosity compensation function, the problem of inaccurate relative density measurement of compound Chinese medicine oral liquid was solved successfully by using Jiahang U-type oscillation densitometer. Enterprises can control product quality more accurately to ensure that the relative density of each batch of products meets the pharmacopoeia standards, which enhances the market competitiveness of products.

Vi. Summary and prospect

The U-shaped oscillation densitometer method added to the 2020 edition of Chinese Pharmacopoeia provides a more scientific, efficient and accurate method for the determination of drug relative density. Shanghai Jiahang Instrument Co., Ltd. U-type oscillation densitometer has been widely used in the pharmaceutical industry due to its advantages of accurate measurement, high efficiency and speed, complete function and compliance with regulations. With the continuous development of pharmaceutical technology and the improvement of drug quality standards, the accuracy and efficiency of relative density measurement will be increasingly high. Shanghai Jiahang will continue to increase investment in research and development, continuously optimize product performance, provide pharmaceutical enterprises with better quality equipment and technical services, help improve the quality control level of China's pharmaceutical industry, and contribute to the protection of public drug safety.