Laser diffraction particle size analysis

Atkinson TW, Greenway MJ, Holland SJ, Merrifield DR, Scott HP. The use of laser diffraction particle size analysis to predict the dispersibility of a medicament in a paraffin based ointment. Spec Publ R Soc Chem 1992 102 139-152. 

Atkinson, T. W., and S. White. 1992. Hydrophobic drug substances The use of laser diffraction particle size analysis and dissolution to characterize surfactant stabilized suspensions. Spec. Publ R. Soc. Chem. 102 133-142. 

Hydrophobic Drug Substances The Use of Laser Diffraction Particle Size Analysis and Dissolution to Characterize Surfactant Stabilized Suspensions... 

Laser diffraction particle size analysis is based on the physical phenomenon that particles in a laser beam scatter laser light at angles that are inversely proportional to the size of the particles [64, 161, 223], Thus, larger particles scatter at small forward... 

This method gives a volume distribution and measures a diameter known as the laser diameter. Particle size analysis by laser diffraction is very common in industry today. The associated software permits display of a variety of size distributions and means derived from the original measured distribution. 

Seven surfactants were selected with differing HLB (Hydrophile Lipophile Balance) numbers and used at concentrations of 0.5 - 2.5% w/v in aqueous solution. An intermediate concentrate was prepared by high shear mixing and subsequently diluted with 1% methylcellulose solution to give a final drug concentration of 10% w/v. Methods of analysis included laser diffraction particle size determination, optical microscopy and dissolution into an aqueous medium. The suspensions were analysed immediately after preparation and after 4 and 96 hours. 

J Ranucci. Dynamic plume-particle size analysis using laser diffraction. Pharm Technol 16 109-114, 1992. 

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

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. 

These practical issues of particle shape and dispersion are not intended to cast aspersions on the laser diffraction technique rather, these factors have been discussed to bring awareness around the analytical results that are obtained when these factors are present. Laser diffraction has proven itself to be a reliable, robust technique for particle size analysis. When the assumption of nonaggregated spherical particles is violated, there are clear manifestations in the calculated particle size distribution. When analyzing drug substances that are used in low-dose solid oral formulations, the impact of these manifestations can be particularly impactful as there is often a limited number of API lots to be used for method development. Therefore, the analyst must be aware of these issues prior to the commencement of method development to avoid these pitfalls. In addition to the information contained in ISO 13320, Snorek et al. have written a summary around the general practices of laser diffraction measurements in the pharmaceutical industry.19... 

Each of the aforementioned techniques is capable of measuring powder that would be used in low-dose, solid oral dosage formulations. The technique must be compatible with the drug substance, and must be capable of producing the information that is needed. For example, if the particle size distribution is needed to ensure dose content uniformity, photon correlation spectroscopy can only provide an average particle size. In this instance, laser diffraction or image analysis would be more suitable techniques. Table 13.1 contains a comparison of the techniques that have been discussed. 

CIPAC, Method MT 187, Particle Size Analysis by Laser Diffraction , accepted as provisional method at the 46th Meeting, Rome, 2002. 

ISO 13320 Particle Size Analysis-Laser Diffraction Methods-Part 1 General... 

Following the progression of particle size analysis, so far we have gotten a perfect sample, uniquely characterized the particle size and done the statistical parameter estimates now we have the tools to look at actual data and methods of measurement. There are many methods for the characterization of particle size and shape however, in this section we will only include methods commonly used by researchers in tableting. The methods covered are microscopy, sieving, and laser diffraction. 

Laser Diffraction Methods Over the past 30 years laser diffraction has developed into a leading principle for particle-size analysis of all kinds of aerosols, suspensions, emulsions, and sprays in laboratory and process environments. 

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. 

Particle size analysis should be carried out on all batches of salt candidates to establish suitable recrystallization procedures. A rapid assessment of both the particle size and crystal habit can be carried out by Scanning Electron Microscopy (SEM). Laser diffraction techniques can provide a rapid assessment of the particle size distribution using less than lOmg of material. It is also useful to retain a photomicrograph for each batch. 

The theory of Mie " is used also in the laser diffraction method for particle size analysis. r In this method, the light scattered by the particles is collected over a range of angles (usually between 1° and 20°) in the forward direction. The corresponding experimental setup is usually... 

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