Japanese Pharmacopoeia6.08Regarding eye dropsSpecification for insoluble particle detection

The detection of insoluble particles in eye drops is to check the size and quantity of insoluble particles in eye drops.

1Instrument

Using a microscope, filter components for retaining insoluble particulate matter and filter membranes for measurement.

（i）Microscope: a microscope equipped with a micrometer system, a moving stage, and an illumination device, and adjustable to100Magnification factor.

（ii）The composition of the filter used to retain insoluble particles: The composition of the filter used to retain insoluble particles includes a filter holder made of glass or a suitable material that cannot cause any malfunction during testing, as well as a clamp. The device needs to be able to install a diameter of25 mmor13 mmThe filter membrane can be used under reduced pressure.

（iii）Experimental filter membrane: The filter membrane is white with a diameter of25 mmor13 mmThe nominal aperture shall not exceed10 μm, and stamped with about3 mmGrid marking. After preliminary testing, no size equal to or greater than should be found on the filter membrane25 μmInsoluble particles. If necessary, clean the filter with water for particle testing.

2Reagents

Particle testing water: Before use, the pore size should not exceed0.45 μmThe filter membrane is used to filter the prepared water. In100 mLIn water, with dimensions greater than or equal to10 μmThe particles do not exceed10One.

3Step by step

3.1Eye drops solution

Carefully perform all operations in clean equipment and facilities with low dust. Install the filter membrane onto the filter bracket and secure it with clips. Rinse the inside of the stent with insoluble particle testing water * and use it under reduced pressure200 mLInsoluble particle testing water20-30 mL/minFilter at a high speed. Apply vacuum until there is no water on the surface of the filter membrane, and then remove the filter membrane. Place the filter membrane in a flat bottomed Petri dish, with the lid slightly half open, and do not exceed50℃Dry the filter membrane at a certain temperature. After drying the filter membrane, place the Petri dish on the microscope stage. Under the tube lamp of the lighting device, adjust the grid of the filtration membrane to the coordinate axis of the microscope, adjust the microscope to obtain the best view of insoluble particles, and then calculate the size of the effective filtration area of the filtration membrane to be equal to or greater than150 μmThe number of insoluble particles, move the mobile station and ensure that the quantity does not exceed1In this case, the particle undergoes size measurement along its longest axis.

Install another filter membrane onto the filtration device and secure it with a clamp, then wet the inside of the filter bracket with a few milliliters of water for particle testing. Clean the outer surface of the container, invert the container several times, and gently mix the sample solution. Remove the lid, clean the outer surface of the nozzle, and pour the sample solution into a graduated cylinder that has been washed clean with water for particle testing. Repeat the process to prepare25 mLTest solution. Pour the test solution along the inner wall of the filter bracket into the filter bracket. Apply vacuum and gently filter to keep the solution on the filter membrane at all times. For viscous sample solutions, dilute with particle testing water or appropriate diluent, and then filter according to the above method. When the amount of solution on the filter decreases, add30 mLUse water or appropriate diluent for particle testing to clean the inner wall of the filter bracket. use30mLRepeat the process with water3Next time. Gently apply vacuum until there is no water on the surface of the filtration membrane. Place the filter membrane in a Petri dish and lower it below50℃Dry the filter membrane at a certain temperature and slightly open the lid. After drying the filter membrane, place the Petri dish on the microscope stage and follow the same microscope operation steps as above to calculate the effective filtration area of the filter membrane that is equal to or greater than300 μmThe number of particles. In this case, the particle undergoes size measurement along its longest axis.

3.2.Dissolved eye drops before use

Dissolve the sample in the prepared solution and perform testing according to the instructions in the aqueous solution for eyes.

3.3.Suspension type eye drops

Follow the instructions in the aqueous solution for eyes. Take from a container that has been thoroughly rinsed with water25 mLConduct particle testing on the sample, add an appropriate amount of suspension agent or sufficient solvent, shake to dissolve the suspended particles, and use this solution as the sample solution. Use a filter membrane that is not affected by the solvent used.

3.4.Eye drops in a single dose container

Follow the instructions in the aqueous solution for eyes and use10Conduct testing on a sample. Using a diameter of13 mmThe membrane filter and diameter are4 mmThe filter bracket is used to retain insoluble particulate matter.

4.evaluate

If per milliliter of insoluble particles (size equal to or greater than)300 μm）The number of calculations does not exceed1The formulation meets the testing requirements.

Solution:

Shanghai Yinhuang Technology Co., Ltd. provides the following products for detecting insoluble particles in eye drops:

YH-MIP-0103Microscopic Counting Insoluble Particle Analyzer

Technical advantages:

√ Fully automated testing system, automatic scanning, automatic counting, automatic report issuance, reducing human operational errors;

√ Fully automatic detection system to reduce eye damage to testers during use;

√ Can distinguish particle properties, identify the source of insoluble particles, and determine whether the particles are metal or fiber;

√ Complies with the requirements of various pharmacopoeias such as the Chinese Pharmacopoeia, the United States Pharmacopoeia, the European Pharmacopoeia, and the Japanese Pharmacopoeia for insoluble particle testing.