Japanese PharmacopoeiaJP17-2.61Discussion on the Specification and Solution of Solution Clarity Inspection

Japanese PharmacopoeiaJP17In<2.61> Turbidity MeasurementThe following explanations are provided in the chapter for measuring the clarity of solutions:

Turbidity measurement is used to determine turbidity (opalescence) to determine whether the item to be inspected meets the transparency requirements specified in purity.

As a rule, visual method refers to the requirements specified in individual monographsof

Japanese PharmacopoeiaJP17-2.61The standard for checking the clarity of solutions proposes two detection methods for the clarity of solutions, namely visual method and photoelectric photometric method. The following will introduce them separately.

1.visual method

This is used to determine the milky white color(Or light color)The degree of opalescence of fine particles. Therefore, the opacities of colored samples are easily measured to be lower, making it difficult to accurately compare their opacities without using reference suspensions of similar colors.

1.1.Reference suspension

Use pipettes to aspirate separately5 mLThe10 mLThe30 mLThe50 mLFumalazine standard solution, diluted separately with water to100 mL, as reference suspensions respectivelyITheIITheIIITheIVShake before use. Reference suspensionITheIITheIIIandIVThe milk luminosity is equivalent to3 NTUThe6 NTUThe18 NTUand30 NTU.

1.2.step

Take enough of the test solution, water, or solvent to prepare the test solution. If necessary, place the newly prepared reference suspension in a separate flat bottomed test tube with an inner diameter15 - 25mm, colorless and transparent, deep40 mmThen observe the contents inside the tube perpendicular to the tube axis under diffused light against a black background. Diffuse light must be able to make the reference suspensionIEasy to separate from the water area, refer to suspended solidsIIEasy to compare with reference suspensionsIDistinguish them.

In this test, when the transparency of the test solution is unclear and it is difficult to determine whether its opalescence is similar to water or the solvent used to prepare the test solution, a reference suspension is used.

1.3.annotation

When the clarity of the liquid is the same as that of water or the solvent used to prepare the liquid, or its turbidity is not comparable to the reference suspensionIWhen more obvious, the liquid is considered“clarify”If the turbidity of the liquid is greater than the reference suspensionIConsider the following: when the turbidity is greater than the reference suspensionIBut not exceeding the reference suspensionIIWhen, it means“Not exceeding the reference suspensionII”. Similarly, when the turbidity is greater than the reference suspensionⅡBut not greater than the reference suspensionⅢWhen, it means“Not greater than the reference suspensionⅢ”When the turbidity is greater than the reference suspensionⅢtime But not exceeding the reference suspensionIV, indicating“Not exceeding the reference suspensionIV”. When the turbidity is greater than the reference suspensionIVWhen, it means“Greater than the reference suspensionIV”.

1.4.Reagent solution

Furmazin Milk Light Standard Solution: Accurately Take3 mLFumalazine reserve suspension, add water until200 mL. After preparation24Use within hours. Shake well before use. The opalescence of this standard solution is equivalent to60 NTU.

Attachment:

Fumalazine storage suspension:to, toward, at, facing25 mLAdd hexamethylenetetramine25 mLHydrazine sulfate, mix well, let stand at room temperature 24 Use after hours. Store in glass containers without surface defects.2Use within a month. Shake well before use. The turbidity of this suspension is equivalent to4000 NTU.

Fumalazine standard solution:to, toward, at, facing15 mLAdd water to the formalin storage suspension until1000 mLAfter preparation24Use within hours. Shake well before use.

2.Photoelectric photometry method

Japanese PharmacopoeiaJP17-2.61According to the standard for solution clarity inspection,Due to the uneven sub visible light density of opalescent solutions and suspensions, turbidity can also be estimated by measuring the absorbed or scattered light through instruments. The photoelectric photometry method can provide more objective measurements than the visual measurement method. Although they can determine turbidity by measuring scattered or transmitted light, it must be specified in a separate testing methodThe measurement system and light source should be used, and in order to compare observation data, the same measurement system and light source should be used.

In each case, the linear relationship between turbidity and concentration must be established through the use of at least4Construct a calibration curve to demonstrate the concentration. For colored samples, due to the absorption of color, both incident and scattered light are attenuated, and the turbidity value is easily estimated to be lower. Transmission is mainly used-Dispersion method.

2.1.Transmittance turbidity method

When light passes through a turbid liquid, the transmitted light is reduced by scattering through particles dispersed in the liquid. When particles with a constant particle size are evenly dispersed, have a small particle size, and have a low suspension concentration, turbidity is linearly related to concentration. Turbidity can be measured by UV spectrophotometry<2.24>Use a spectrophotometer or photoelectric photometer for measurement. The turbidity of samples with higher concentrations can also be measured, but it is easily affected by the color of the sample, usually in660 nmMeasure left and right to avoid interference caused by color absorption.

2.2.Scattered light turbidity method

When the suspended particles are at a right angle to the incident light direction, the light rays of the suspended particles refract(the Tyndall effect)The suspended matter appears milky white. The light entering the turbid liquid is partially transmitted, partially absorbed, and the remaining part scattered by suspended particles. The scattered light measurement method displays the units of scattered turbidity within the low turbidity range(NTU)The linear relationship between the value and the relative detector signal. As the turbidity increases, not all particles are exposed to the incident light, and the scattered radiation of other particles will be hindered in reaching the detector.

2.3.Ratio turbidity method

This method measures both scattered light values and transmitted light values simultaneously, and turbidity is determined by the ratio of scattered light values to transmitted light values. This program can compensate for the reduced light caused by sample color and eliminate the influence of color. When using an integrating sphere for measurement, particularly known as the integrating sphere method, it measures the total transmitted light value and scattered light value of suspended particles, and the turbidity can be determined by their ratio.

2.4.Application of Photophotometry in the Requirements of Monographs

The turbidity of the test solution measured by photoelectric photometry can be used as an indicator standardBy using a reference solution with known turbidity, such as a reference suspensionI-IVIf necessary, water and solvent solution can also be usedNTUTransfer data for the unit. In the automatic compensation device calibrated using a reference solution with known turbidity, the measurement results are as follows:NTUGiven as a unit and can be directly compared with the required specified value.

Often used in turbidity measurementNTUAs a unit. It is for measurement purposes90±30The unit used to obtain turbidity information from scattered light on incident light intensity, using a tungsten lamp860 nmInfrared measurement90±2.5°The scattered light affects the intensity of the incident lightwithFNUFor the unit. Within a smaller measurement range(less than40 NTU)，FNUequivalent toNTUThe concentration unit of Fumalazine is also usedFTUThat is1LPure water1 mgThe suspension of fumarate is1 FTU.

Solution:

Shanghai Yinhuang Technology has launched the following products for clarity inspection of pharmaceuticals, which also meet the requirementsJapanese PharmacopoeiaJP17-2.61Specification for checking the clarity of solutions.

1Special umbrella shed light for clarity inspection

HN-100AType andHN-200AThe specialized umbrella shed lamp for clarity inspection meets the instrument requirements for visual method detection of solution clarity in various pharmacopoeias. It has a light source of light forest belt type, which can effectively reduce the stimulation of light on the eyes during visual inspection. Its illuminance can reach up to5000 LuxAmong themHN-200AType specific umbrella shed light has been addedRGBTri color light source can be used for clarity detection of colored samples.

2TheYH-CLS-1201Clarity inspection analyzer

This instrument adopts a full-color LCD touch screen for operation and control, which can directly detect the clarity of injection raw materials and injections, and has four levels of permission management and audit tracking functions*GMPThe requirement for data integrity is an effective instrument for evaluating liquid consistency.