Selection of laser particle size analyzer in the pharmaceutical industry

The pharmaceutical dosage form is the form in which the drug is present and administered to the body. In today's various conventional pharmaceutical dosage forms, 70% of the active ingredient is present in the form of a powder in tablets and capsules. For other forms, intermediate products or excipients are also often present in the form of a dry powder. In addition, from the recent development of new microcapsules, microspheres, powders, liposomes, new emulsions and nano-particles, the physical properties of various drug particles are the key parameters affecting the quality of the drug. Therefore, as the authoritative technology for measuring various physical properties of particulate matter---laser particle size technology, it is increasingly valued by engineers and technicians and drug inspectors who are quality control in the research and production process of pharmaceutical preparations.

Many users now find it very difficult to pick a laser particle size analyzer. Because on the one hand, there is not much understanding of the laser particle size analyzer; on the other hand, the market is mixed, and each manufacturer says that its particle size analyzer is the best, and I don’t know who to listen to. This article gives some points of reference here:

First, the selection of laser particle size analyzer must first pay great attention to the accuracy and repeatability of the instrument. Because the particle size analyzer is a precision instrument that measures the particle size range, if its test accuracy is not good and the repeatability is poor, then you should not choose a laser particle size analyzer. Because this will give you the wrong data, can not give guidance to your production and process, and then delay your processing. What's more, an inaccurate laser particle size analyzer can cause you to return, lawsuit, or make you a failure with your supplier.

Second, the choice of laser particle size analyzer must first look at the technical strength of its manufacturers, how to judge the technical strength of manufacturers? First of all, who is the main inventor, and how well is it in the particle world? Is it an expert in this field, if its manufacturer can't say the name of the inventor and the technical level, you should be careful, some may be infringing products, and buying such a product will in turn infringe and cause a lawsuit. Moreover, this kind of manufacturer is not long-term. If you buy this kind of product, you will be affected by it and you will not get long-term technical support.

Third, the better theory for testing submicron and micron laser particle size analyzers is the full-range Mie scattering theory. If the manufacturer does not have a high level of technicians, it is impossible to study the digital model of the whole process of Mie theory. A little something can't solve the fundamental problem. Whether the resolution can be resolved by testing with submicron standard particles.

Fourth, to understand how the dispersion is, a sample to get an objective test results, only the dispersion is good, in order to measure the correct results. If the dispersion system can't keep the sample in the dynamic test all the time, or the pipe passing through the particle is too long to precipitate the large particles quickly, the information captured by the large particles is less, and the information of the small particles is relatively more, the actual measured data. It will be too small, it is not objective data, and there is no practical guiding significance. Some manufacturers hope that the data measured by their products is as small as possible, but if it is not objective data, it may lead to economic disputes.

5. Several key test points for the pros and cons of the product.

The laser particle size analyzer has several key test points, as follows:

1 Particle size measurement range
Wide range of particle sizes, suitable for a wide range of applications. Not only depends on the range reported by the instrument, but how the small particle scattering beyond the main detector area is detected.
The best way is to have a full range of direct tests to ensure consistency in the background subtraction. The hybrid test of different methods, and then using a computer to fit into a map, will definitely bring errors. The LS laser particle size analyzer (Beckman Coulter, USA) has a detection range of 40 nm to 2000 μm, which plays an important role in particle analysis in new formulation studies.
2 laser light source Generally choose 2mW laser, the power is too small, the scattered light energy is low, resulting in low sensitivity; in addition, the gas source has a short wavelength and stability is better than the solid light source.
3 Detector Because the larger the radius of the laser diffraction aura, the weaker the light intensity, it is easy to cause the small particle signal/noise ratio to decrease and miss detection. Therefore, the detection of small particles can reflect the quality of the instrument. The development of the detector has gone through several stages of round, semi-circular and fan-shaped.
3.1 The latest generation of detectors from Malvern, UK, adopts a patented non-uniform cross-arranged three-dimensional sector detection system with the highest actual resolution and no signal dead zone, which is equivalent to 175 circular or cross-shaped arrays and 93 semi-circular arrays. The direct detection angle is 135 degrees.

3.2 Number of Channels In the laser particle size analyzer, unlike the concept of a channel in a counter, it is actually the number of areas of the detector. It has a theoretical and practical optimization value: less: the received scattered light is not sufficient, the accuracy is poor; more: the sensitivity is too high, resulting in poor reproducibility.
In order to compensate for the short sampling speed, some manufacturers use more channels to achieve reproducibility and achieve sensitivity requirements. Therefore, such measurement time is 20 seconds or more.
Malvern Instruments' latest generation of Mastercizer 2000 laser particle size analyzers sample 1000 times per second with a measurement time of only 2 seconds (2000 results average), which optimizes accuracy and repeatability.
4 Whether to use the full Mie theory because the Mie's theory of light dispersion is very complicated and the data processing capacity is large, so some manufacturers ignore the optical properties such as the refractive index and absorption of the particles themselves, and adopt the approximate Mie theory, resulting in limited application range. Increased chances and other issues.
5 Accuracy and repeatability indicators The higher the accuracy and repeatability indicators, the better. NIST standard particle detection was used.
6 Stability Instrument stability includes the stability of the optical path and the stability of the dispersion system and the surrounding environment. Generally, a gas laser is used, and an optical platform is used to contribute to the stability of the optical path. Internal heating components (such as 50 watt tungsten lamps) will affect the environment around the light path.
The stability index is not included in the manufacturer's instrument description. The user can only judge by judging the structure of the instrument and visiting or asking other users who have used it for a long time.
7 Scan speed Fast scan speed improves data accuracy, repeatability and stability. The scanning speeds of instruments from different manufacturers vary from 1 time/second to 1000 times/second. In general, the more the number of cyclic scan tests, the better the accuracy of the average results, so the higher the speed, the better; the jet dry method and spray require the higher the speed, the better; the free fall method is not fast, but the speed is not fast, but Since the particles pass only through the sample area once, the speed is also faster. The amount of sample a user needs to process each day is also a factor in considering speed.
8 can be automatically centered, no need to change the lens, can be automatically corrected
9 Simplicity of use and maintenance In this regard, it is often overlooked before purchase, but in fact directly determines the efficiency and longevity of the instrument. The way to understand is to understand the structure of the instrument and other existing users.
It is convenient to disassemble and clean: the particle size analyzer is divided into two parts: the main unit and the disperser. The sample flow cell always needs to be cleaned regularly, and the cleaning interval depends on the nature of the sample. Instruments that combine the main unit and the disperser often place the sample cell deep inside the instrument, which is cumbersome to remove and disassemble, and can easily damage the optical path system.
10 Compliance with international standards The ISO 13320 standard is a basic requirement for laser particle size analyzers. But not all manufacturers follow this standard. In the measurement of submicron particle distribution, the non-laser diffraction method is not in accordance with ISO13320.
11 diffuser
11.1 Whether the wet method has physical dispersion functions such as ultrasonic and stirring, whether the ultrasonic power and the stirring speed are continuously adjustable is the key to ensure the repeatability of the analysis results.
11.2 Is the dry method closed measurement, is the sample easy to disperse? If not, is the jet disperser selected? The 300 m/s impingement gas flow is a prerequisite for ensuring that the sample can be fully dispersed to obtain a true analysis result.