LASER Diffraction

Laser Diffraction, also known as Static Light Scattering, has become one of the most widely used particle sizing distribution techniques across various industries. Samples can be analyzed on either a liquid suspension or dry dispersion basis. The sample material is passed through a laser beam which results in the laser light scattered at a wide range of angles. Detectors placed at fixed angles measure the intensity of light scattered at that position. A mathematical model (Mie or Fraunhoffer Theory) is then applied to generate a particle size distribution. The final result is reported on an Equivalent Spherical Diameter Volume basis. Particle Size by Laser Diffraction is widely recognized by numerous standards and guidance agencies such as the ISO, ASTM, USP, EP and JP. This techniques ability to perform dry or liquid dispersion analyses make it a good choice for general particle sizing applications and its broad dynamic range (submicron to millimeters) has proven useful to the environmental, pharmaceutical, food, health, beauty and many other industries. A wide variety of sample types are applicable to analysis by Laser Diffraction including active pharmaceuticals (APIs), excipients, flyash, turbid wastewater, and environmental emission samples. Common applications include QA/QC batch testing, general survey screening measurements and comparative studies. Electrozone (Coulter Counter Technique)

Electric Sensing Zone is also referred to as the Coulter Technique or Coulter Counter. The instrument is a true high resolution, high speed particle counter and particle size distribution analyzer that covers a nominal span of about 1.0 um to 300um. Under special circumstances, the lower detection level can be reduced to about 0.4 um. Data is typically presented to our clients on a Frequency (Population) and Volume (Mass) basis vs. Size. Being a true particle counter, the instrument can also be used to determine the concentration of Particles/mL of Fluid vs. Size. Particles suspended in a conductive fluid (aqueous or organic) are drawn through a precision sapphire aperture on either side of which are two platinum electrodes. A constant current is impressed upon the electrodes which results in a constant voltage across the aperture. Upon the passage of a particle through the aperture, a voltage pulse is generated due to the change in electrolyte resistance. The change is proportional to the volume of the particle. Therefore, the analytical method determines the envelope volume of a particle in three dimensions which is the instruments claim to fame. The signal is counted as one event (i.e. particle count) and simultaneously, the volume is directly determined. Also, data presented on the basis of Equivalent Spherical Diameter is enhanced because there are no optical theories of light involved in the measurement principle. Light Obscuration / Photozone

Light Obscuration, also referred to as Photozone and Single Particle Optical Sensing (SPOS), is an analytical technique of high resolution capable of detecting a small percentage of outliers. It can also be used to obtain an overall size distribution, when operated with proper technique. An important consideration when choosing Light Obscuration is the concentration of the sample presented to the instrument. The sample must be in a dilute form (either as received or prepared by PTL) for analysis. The technology works by passing a dilute stream of particles in a liquid suspension between a light source and a detector. The light source in this case is a laser diode, which illuminates the individual particles in the stream and results in a shadow or blockage of light on the detector. This light blockage is termed obscuration. The detector measures this reduction in light intensity and using a calibration curve; processes the signal to determine the size of the particle. For smaller particles (i.e. approximately <2 m) a light scattering detector measures the increase in light intensity scattered over an optimized range of predetermined angles. The signal is also counted as a single event, thus this technique is able to provide true particle counts as it analyzes individual particles. The results can be reported on a Number and/or Volume weighted basis, using the classic assumption of Equivalent Spherical Diameter. Light Obscuration is another widely accepted particle sizing technique in many fields. Fields ranging from pharmaceuticals to hydraulic/lubrication applications can utilize the particle counting and sizing capabilities of Light Obscuration. The technique is recognized by the ISO, USP and ASTM for example as an appropriate method for measuring the size and number of particles in samples such as: injectables, ophthalmic solutions, industrial oil/lubricates and even dilute waste/process water studies. Numerous carrier fluids, both organic and inorganic can be used with the instrumentation. PTL has

utilized Light Obscuration to solve numerous pharmaceutical and industrial problems for clients over the years. Photon Correlation Spectroscopy/Dynamic Light Scattering

Dynamic Light Scattering (DLS) is a commonly used term to describe a technique which measures the particle size and estimated distribution of submicron particulate systems. In addition, the terms Photon Correlation Spectroscopy (PCS) and Quasi-Elastic Light Scattering (QELS) have also been used historically to refer to the same analytical principle. By any name, the technique is widely recognized throughout the pharmaceutical and industrial world reflected in the existence of several standards describing the technique (i.e. ISO 22412, ISO 13321, and ASTM E2490-09). Dynamic Light Scattering requires particles approximately less than a micron in size to be homogenously suspended in a fluid (aqueous or organic). A few examples of suitable systems could include aggregated proteins, pigment components, micelles or emulsion droplets suspended in a continuous phase. The nano-dispersed system is placed into the optical path of a LASER. The LASER is then scattered upon interacting with the particles in the suspension which are moving by Brownian Motion. The scattered light is captured by a detector over the course of the analysis to determine the rate of diffusion (i.e. how fast the particles move within a system due to Brownian Motion) and the average Hydrodynamic particle size (referred to as the Z-Average) is calculated on an Intensity weighted basis using the Stokes-Einstein equation. In simple terms, small particles move/diffuse more rapidly than larger particles. While other reporting formats are available, the most widely accepted and recommended way to report results from DLS is on an Intensity basis using the Z-Average along with the Polydispersity Index (PDI). The PDI is an indicator of the broadness of the particle size distribution. While the technique is straight forward in principle, achieving representative results relies on knowledge of the dispersed system (such as optical parameters of the particle/liquid and viscosity of the dispersed system). In addition, optimal results require an understanding of the strengths and limitations of the DLS instrument being used. Different instrument manufactures vary certain aspects of the data acquisition process such as the angle of detectors or the data processing algorithms. These variations can generate different results between instruments or require a need to alter sample preparation and concentration. Sample preparation is of the utmost importance in DLS analyses as the analytical principle assumes an infinite dilution in an attempt to limit the effect of particle/particle interactions. As a result, depending on the instrument and sample properties, dilution of the sample is sometimes necessary for analysis. However, this requires careful thought and consideration in proper method development as to not destabilize the dispersed system. PTLs years of experience in sample preparation and variety of inhouse DLS equipment allows us to assist with all aspects of our clients projects and provide solutions. We have the expertise necessary to develop and validate an accurate, precise and robust method for your submicron sized samples.

Sieve Analyses

Sieving has been around since the time of the Egyptians and can be considered the backbone of particle size technology. Sievings continuing popularity is due to the techniques fundamentally simple principle and methodology, historical reference, and cost effectiveness. Several instrument components involved in a sieve analysis can be quality controlled, making the technique applicable to various industries including pharmaceutical, industrial, agricultural, and chemical. A sieve analysis consists of using a single or set of screens (typically woven wire mesh), decreasing in opening size, to separate or classify a sample. Several mechanisms are used to disperse the sample and transport it through the screens (i.e. vibration, air entrainment or flowing liquid). While considered relatively low resolution, sievings practical applications lend itself well to quality control specifications. ASTM E-11 establishes acceptance criteria for the woven wire mesh opening tolerances of standard sieve sizes. For optimal quality control, PTL verifies its in-house sieves with an external vendor for compliance with the ASTM E-11. While sieving may appear rudimentary compared to more modern instrumental particle characterization techniques, it still requires several important considerations to obtain the best repeatable and precise results. Several factors must be considered when developing a robust sieving method or performing a routine quality analysis. Sample size, sieving duration, controlled agitation parameters and end point determination are all critical method variables which need to be addressed. PTLs various sieving capabilities and strict attention to detailed procedures, which incorporate the topics above, ensure that the best possible results are generated. Some sample properties (such as hygroscopic or electrostatic tendencies), can pose significant analytical difficulties, especially at small sieve sizes. As a result, using an appropriate sieving technique is of utmost importance. Such sample types may be suspended an inert liquid media prior to analysis or aided with flow enhancers. Sieve results are reported as the differential weight percent retained on each sieve as well as the cumulative weight percent less than the sieve size. Specific reporting requirements are easily adjusted based on the clients request. For more information on how PTL can employ sieving to assist with quality control specifications, third party verification, method development and/or transfer please give us a call. Air Permeability Diameter

This classical analytical technique determines the average particle size by measuring the pressure drop across a packed powder bed using a water manometer. The pressure drop is a function of the permeability of the packed bed. This is related to the surface area of the particles which is then

transformed to an average size based upon the assumption that the particles are spherical. The disadvantage of the technique is that it does not report on the statistics of the size distribution.

Fisher Sub-Sieve Sizer - The Fisher Sub-Sieve Sizer tests powders quickly and reproducibly for their Average Particle Diameter - also known as the Air Permeability Diameter.

Particle Size and Shape Analysis Image Analysis is a powerful analytical technique which can provide additional information on a sample compared to just particle size and distribution. The majority of particle sizing techniques assume an equivalent spherical diameter of some measured property. This simplification is advantageous as a sphere is the only shape which can be described using a single number (i.e diameter). This assumption is acceptable in many applications where a comparison between samples is needed. In real world applications, particles are seldom spherical and cannot truly be described with a single number. The additional parameters provided by image analysis can help provide further insight into important properties which can affect dissolution, flowability, processing differences and material handling issues of a sample. Image Analysis involves digitally capturing images of a sample using a CCD camera. The digital image is composed of pixels and each pixel is assigned a value. This array of pixels is then evaluated and a process referred to as thresholding occurs. Thresholding is performed within the image analysis software package and assigns a value where by each pixel measured is compared and thus treated as particle or considered as background (non-particle). Once thresholding has been performed and the system calibrated using NIST traceable standards, measurement of the digital image is performed. Upon completion of the measurement, results are available on numerous shape and size parameters; such as Aspect Ratio, Sphericity/Roundness, Solidity, Convexity, and Circular Area Diameter.along with numerous others. The numerous shape parameters and output formats available in modern Image Analysis software can provide exciting new ways for PTL to evaluate a clients sample. As in any analytical technique, sample preparation is extremely important. Image Analysis requires an understanding of the question at hand and proper treatment of the sample. Since Image Analysis is considered a true particle counting technique, the higher resolution/sensitivity can increase analysis time in order to count a statistically significant number of particles. Even with modern automated image analysis systems, which attempt to overcome these limitations, the analysis time for an image analysis measurement is greater than other particle sizing techniques. Coincidence (over lapping of discrete particles) or improper use of thresholding and imaging filters can adversely affect results and need to be considered during the measurement.

PTL has used Image Analysis since our companys inception to solve client problems and provide innovative solutions to their projects. PTLs years of experience with Image Analysis and stringent quality system allow our clients to have the highest confidence in the results provided. Contact us to discuss how Image Analysis may be a valuable tool to evaluate your samples.