USP787- Detection of insoluble particles and foreign objects in therapeutic protein injections uses two methods for detecting insoluble particles. However, in the European Pharmacopoeia, USP1788, and Japanese Pharmacopoeia, it is recommended to use microscopic counting method for the examination of insoluble particles and foreign objects in injection solutions.

In the past three years, due to the prevalence of the epidemic, more and more office work and learning rely on the Internet and mobile phones, followed by an increase in ophthalmic diseases. With the improvement of people's awareness and attention to health, the current society is paying more and more attention to the safety of eye drops. Among them, there are clear standards for particle foreign body examination in the Japanese Pharmacopoeia and the United States Pharmacopoeia, as well as recommendations for microscopic counting as an important examination method to ensure that approved ophthalmic solutions do not cause secondary harm to the human body.

As an important source of insoluble particles in medicine, pharmaceutical packaging materials have attracted the attention of R&D and production personnel. The cleanliness of pharmaceutical packaging materials directly affects whether the insoluble particles and foreign objects in drugs exceed the standard. The microscopic counting method insoluble particle analyzer can accurately check the quantity and size of insoluble particles and foreign objects in pharmaceutical packaging materials, and can clearly see the morphology of the particles and foreign objects, providing corresponding reference standards for R&D and production personnel.

There are clear regulations in the pharmacopoeia regarding the detection indicators of insoluble particles in injections, such as the Chinese Pharmacopoeia 0903- Insoluble Particle Detection Method, the Japanese Pharmacopoeia 6.08 Insoluble Particle Detection Specification for Eye Drops, the European Pharmacopoeia 2.9.19 Sub Visible Particle Detection Specification, the USPParticle Detection Specification for Injectants, and the USPParticle Detection Specification for Eye Drops, all of which have corresponding requirements for the detection of insoluble particles in injections.

Due to the fact that drugs mainly diffuse and release through microporous membranes, and then enter the capillary plexus through the skin to exert their effects, the harm of particles is particularly concerned. Conventional microscopic particle inspection is no longer suitable for the current fast-paced research and experimental process, so the microscopic counting method insoluble particle analyzer has emerged. One experiment can not only measure the number of particles, but also directly provide the corresponding proportion of particles with different sizes.

In the 2020 edition of the Chinese Pharmacopoeia "0109 Ointment and Cream", it is stated that particle size testing is a mandatory item for this type of preparation. The Pharmacopoeia also specifies how to conduct this test, and the first method (microscopic method) in the general rule "0982 Particle Size and Particle Size Distribution Determination Method" should be used for determination.

The main active ingredients in protein injection are peptide proteins. Compared with small molecule preparations, these drugs have the characteristics of high activity, low toxicity, strong specificity, and are conducive to clinical application, and have a wide range of application prospects. Due to the special properties of this type of preparation, a certain degree of stress can cause a large number of bubbles to be generated (as shown in Figure 1). When using the photoresist method to detect insoluble particles in this type of preparation, significant false error results will be produced. Therefore, using the microscopic counting method for insoluble particle detection in this type of preparation is *.

Suspension type injections are generally used for intramuscular injection, which are usually water-insoluble drugs or drugs that require prolonged efficacy after injection. After forming a suspension, they present an opaque appearance. The section of the United States Pharmacopeiastates that when the sample presents a milky white morphology, it is not suitable to use the photoresist method for insoluble particle detection. In this case, the microscopic method should be used for insoluble particle detection.

The testing principle of the photoresist method is that when laser is irradiated on a flow cell, particles passing through the flow cell will cause a light attenuation signal, which will be converted into electronic pulses, recorded, and related to the equivalent circle diameter of the particles. The optical impedance method can only measure particles that are opaque or have a refractive index significantly different from the surrounding liquid. When the sample appears milky white, abnormal refractive index can cause deviation in the test results. When using microscopy to detect such formulations, it can directly avoid erroneous results based on testing principles.

Plastic particle pollution generally occurs when sharp objects are used through injection ports or from plastic infusion sets. Inserting a needle into the septum or stopper of a medication bottle or infusion container may result in fragments separating from the septum or stopper. The particle may float in the injection solution. If the fragments are small or covered (such as labels or colored vials), contamination may not be detected and may be inhaled into the syringe for injection into the patient's body.

ZETA potential refers to the potential of the shear plane, also known as electromotive potential or zeta potential, and is an important indicator for characterizing the stability of colloidal dispersion systems. The significance of Zeta potential lies in the positive correlation between its absolute value and the stability of the detection object. Zeta potential is a measure of the strength of mutual repulsion or attraction between particles. To some extent, the smaller the molecule or dispersed particle, the higher the absolute value of Zeta potential, and the more stable the system.

The YH-FIPS-10 flow dynamic image method particle size analyzer (as shown in Figure 1) is an instrument that uses a high-speed camera to collect real-time images for particle analysis. The sample is recorded and photographed in real-time during the flow process, and enough particle images can be collected (as shown in Figure 2). The test results are representative and statistically significant. It can accurately capture the morphological characteristics of different particles in the actual production process, thereby improving the stability, solubility, and flowability of the product.