How to choose the appropriate method for insoluble particle inspection: discussion on microscopic counting method and photoresist method testing

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 USP<788>Particle Detection Specification for Injectants, and the USP<789>Particle Detection Specification for Eye Drops, all of which have corresponding requirements for the detection of insoluble particles in injections.

There are two types of insoluble particle inspection methods, namely photoresist insoluble particle inspection and microscopic counting insoluble particle inspection. How to choose the appropriate equipment? The commonly used photoresist method is an insoluble particle analyzer, which typically consists of a sampler, sensor, and data processor. When the results of the light resistance method do not meet the requirements or the test sample is not suitable for the light resistance method, the microscopic counting method should be used for determination, and the results of the microscopic counting method should be used as the basis for judgment. The photoresist method is not suitable for formulations with high viscosity and easy crystallization, nor for injections that are prone to bubble formation when entering the sensor. For such formulations, microscopic counting method is required for measurement.

Below, I will demonstrate the advantages and disadvantages of two instruments, namely the photoresist insoluble particle analyzer and the microscopic counting insoluble particle analyzer, in detecting insoluble particles in injection solutions based on their instrument characteristics

test method	Photoresist method	Microscopic visual method	Microscopic Counting Insoluble Particle Analyzer
principle	The blocking effect of particles on light	Eye comparison	CCD camera automatic detection
Testing Scope	1-400μm	＞ 1 μ m (based on magnification)	＞ 1 μ m (based on magnification)
precision	high	Very low	higher
applicability	Ordinary injection solution	All tested drugs are applicable	All tested drugs are applicable
advantage	Fast detection speed high efficiency	NA	Graphics and visualization high precision Artificial intelligence particle classification
shortcoming	There may be false results Large usage Not applicable for special dosage forms	Easy to miss detection Low accuracy visual fatigue	Compared to the photoresist method, the detection time is longer

Below, I will use two instruments to conduct insoluble particle tests on Yibao brand purified water and a certain brand eye drops:

1、 Inspection results of insoluble particles in Yibao brand purified water:

1. Photo resistance method inspection result chart:

2. Microscopic counting method inspection result chart:

It can be seen that in the detection of pure water, the photoresist method can avoid the introduction of foreign particles and quickly obtain accurate experimental results. In this case, the photoresist method is preferred.

2、 The test results of insoluble particles in a certain brand's eye drops are as follows:

1. Photo resistance test result chart:

2. Microscopic counting method test result chart:

The following figure shows the product image

From the above data, it can be seen that the magnified inspection results of three times the number of bubbles and additives such as silicone oil in eye drops result in unqualified inspection results. At this time, microscopic counting method insoluble particle inspection is required. In the current era of strong regulation in pharmaceutical research and development, production, and marketing, pharmaceutical companies hope to have a clear view of the morphology of particles contained in drugs under development, in order to distinguish whether particles should be avoided and treated.

The following figure shows the particle morphology of the sample particles under the microscope counting insoluble particle analyzer: