Laser diffraction instrument

Particle Size Laser Refractometiy is based upon Mie scattering of particles in a liquid medium. Up until about 1985, the power of computers supplied with laser diffraction instruments was not sufficient to utilize the rigorous solution for homogeneous spherical particles formulated by Gustave Mie in 1908. Laser particle instrument manufacturers therefore used approximations conceived by Fraunhofer. 

Several groups have investigated the effect of surfactants on emitted droplet size. In the early work performed by Polli et al., the surfactant sorbitan trioleate decreased the MM AD of the CFC dexamethasone suspension when added to the formulation (52). A suspension of terbutaline in a CFC system containing sorbitan trioleate surfactant was shown to have little change in emitted particle size when either 2.8 or 14mg/mL of surfactant was added (53). Interestingly, the surfactant had a significant effect on the obscuration (droplet concentration) of the laser diffraction instrument used to determine particle size. Surfactants may lead to an increase in MMAD due to decreased evaporation rates from aerosol droplets. This may occur because of their tendency to associate at the air liquid interface (54). 

Figure D3.3.1 Schematic diagram of laser diffraction instrument for determining droplet size distribution.

Calibration standard containing particles of known diameter (see recipe) Laser-diffraction instrument designed for particle size analysis (e.g., Mastersizer, Malvern Instruments)... 

Turn on the laser diffraction instrument and allow it to warm up for 30 min before taking measurements. 

Laser diffraction is most suitable for analyzing dilute emulsions that are fluid, and therefore competes directly with electrical pulse counting methods, which are applicable to similar systems (see Alternate Protocol). Most laser diffraction instruments can cover a wider range of particle sizes (i.e., 0.01 to 1000 pm) than electrical pulse counting instruments (i.e., 0.4 to 1000 pm using a number of different aperture sizes), and do not require the presence of electrolyte in the aqueous phase, which could destabilize some electrostatically stabilized emulsions. Nevertheless, electrical pulse counting techniques are considered to have greater resolution. 

The accuracy to which the droplet size distribution of an emulsion can be determined by a properly functioning and correctly operated laser diffraction instrument depends upon two major factors (1) the design of the optical system used to measure the diffraction pattern resulting from the transmission of a laser beam through the cuvette and (2) the sophistication... 

For the reasons described above, the droplet size distribution of the same emulsion measured on different laser diffraction instruments can be significantly different, depending on the precise design of the optical system and the mathematical theory used to interpret the diffraction pattern. It should be noted, however, that the most common source of error in particle size analysis is incorrect operation of the instrument by the user. Common sources of user error are introduction of air bubbles into the sample, use of the wrong refractive index, insufficient dilution of emulsion to prevent multiple scattering. and use of an unclean optical system. 

Gustav Mie was able to solve this equation for. Sj(0) and S2(6) using a rigorous mathematical solution, assuming the scattering objects were spheres.8 To apply Mie s solution to the scattering equation, as most laser diffraction instruments do, the refractive index of the material must be known (both the real and imaginary component) The refractive index is expressed as ... 

Unfortunately, this is not an atypical situation. APIs frequently exhibit rod- or needle-like morphology. Using laser diffraction instruments, particle size distributions of these materials appear as multimodal, making it difficult to assert that... 

Dispersion Sonication of the sample should be avoided if at all possible. Dispersion should be accomplished through the selection of an appropriate surfactant and the mechanical agitation that is available with the stirring and pump settings on the laser diffraction instrument. 

Heffels C, et al. 1996. Correction of the effect of particle shape on the size distribution measured with a laser diffraction instrument. Part. Part. Syst. Charact. 13 271-279. 

The newer la.ser diffraction instrument allows measurement for particle sizes ranging from 0.1 pm to 8 mm (7). Most of the laser diffraction instruments in the pharmaceutical industry use the optical model based on several theories, either Fraunhofer, (near-) forward light scattering, low-angle laser light scattering, Mie, Fraunhofer approximation, or anomalous diffraction. These laser diffraction instruments assume that the particles measured are spherical. Hence, the instrument will convert the scattering pattern into an equivalent volume diameter. A typical laser diffraction instrument consists of a laser, a sample presentation system, and a series of detectors. 

Figure 30 shows a simple model of a typical laser diffraction instrument where the diffraction pattern of light scattered at various angles from the sample particles that pass through the He-Ne laser beam is measured by different detectors and recorded as numerical values relating to the scattering pattern. These numerical values are then converted to the particle size distribution in terms of the equivalent volume diameter using a mathematical model from the instrument s software. 

RGURE 30 A simple model for a typical laser diffraction instrument. 

Fnrthermore, for dosage consistency, there is a need for an aerosol formulation to be monodispersed [4]. The particle size distribution of an aerosol is defined by its geometric standard deviation (GSD). The GSD is the ratio of particle diameters at 84% and 50% cnmnlative mass of particles or the ratio of the particle diameters at 50% and 16% cnmnlative mass of particles when the cumulative mass of particles is plotted against the eqnivalent diameter on a log-probability scale following particle size analysis nsing either impactors or laser diffraction instruments. 

Since the initial introduction of laser diffraction instrumentation in the 1970s, many different applications to panicle si/e aniilysis have been reported. Ihese have included measurements of si/e distributions of radioactive tracer particles, ink particles used in photocopy machines, zirconia fibers, alumina particles, droplets from electronic fuel injectors, crystal growth particles, coal powders, cosmetics, soils, resins, pharmaceuticals, metal catalysts, electronic materials, phoiugraphic emulsions, organic pigments, and ceramics. About a dozen instrument companies now produce LALLS instruments. Some I.AI.LS instruments have become popular as detectors for size-exclusion chromatography. 

IS (a) i se an Internet search engine to find laser diffraction instruments made by a commercial company (try Malvern, Sympatee, Shimadzu, Beckman Coulter, or Horiba), Choose a specific insirumcni and describe its operation What laser is used What is the detection system Give typical values of accuracy and precision. 

A final lesson is illustrated in Figure 12.10, which shows tributions obtained by two well-known commercial laser diffraction instruments, but using different saii le preparation techniques. Sample A was not sonicated, vdiile sample B was sonicated for 3 min. Clearly, very different results are produced which do not reflect the capability of the two different instnunents and could easily be misinteipreted. 

Fig. 2.12 Classical set-up of laser diffraction instruments (left) and demonstration of laser diffraction by illuminating a thin layer of monodisperse silica powder ( Benno Wessely 2004)...

G.2 Laser Diffraction. There are now a large number of laser diffraction instruments on the market. This is an excellent technique, provided that a representative sample can be obtained and placed in the instrument. A key difficulty is sampling successfully (i.e., without altering the droplet size) and representatively, particularly at high concentrations when stabilization and dilution are often required. 

Fig. 13.16 Typical set up of the laser diffraction instrument. The figure is reproduced from Merkus [136] with permission from Springer...

Setekleiv and Svendsen [180] used the same laser difliraction particle sizer to characterize the ability of mesh pads to separate droplets from the gas stream in a scrubber. Droplets in the size range 30-1000 p,m with a bi-modal distribution was obtained at low pressure. A rough sketch of the mounting of the laser diffraction instrument used in this work is shown in Fig. 13.17. Numerous applications of the LD particle sizer for solid particle size distribution measurements characterizing aerosols and suspensions can be found in the literature. Only a few examples of laser diffraction solid particle size distribution measurements relevant for fluidized bed system characterization are mentioned in this report. Garea et al. [71] measured the solid sorbent particle size distribution in a fluidized bed in-duct desulfurization reactor under in-duct conditions by laser diffraction. Ferrer et al. [66] studied fluidized bed combustion of refuse-derived fuel in presence of protective coal ash and measured the fly ash particle size distribution with a laser diffraction method. Tanneur et al. [192] measured the solid particle size distribution in a fluidized bed by use of a diffraction particle size analyzer. 

We can see from the above table that the mean sizes can be quite different if one uses an electron microscope ( D, o= 4.00), or a laser diffraction instrument ( D4,3 = 9.74) to measure this four-particle system. The difference between a number-averaged mean (q = 0) and a mass-averaged mean (q = 3) resides in the fact that in the number average the mean value represents values from particles with the largest population while in the mass average the mean value represents more from particles with the largest size. The same is true for a real distribution. A number distribution may be completely different from its corresponding mass... 

Figure 3.1 shows the generic setup of a laser diffraction instrument and the major functions of each element along with the section number in this text where a more detailed description can be found. 

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