The US Pharmacopeia contains several particle sizing procedures with drug safety in mind including USP <788> and USP <729>. USP <729> requires that the mean droplet size as well as the extent of the large-diameter droplet tail (> 5 µm) be determined. Conventionally, a method such as dynamic light scattering would be used to determine the mean droplet size and a light obscuration technique would be used to analyze the large-diameter droplet tail. It has been found that by using the FX-Nano system, which uses focused beam light obscuration, it is possible to determine both the mean diameter and large-diameter droplet tail using one characterization technique. This is the first single instrument that would satisfy the requirements for USP <729>.
The new focused light obscuration technique extends the lower limit of SPOS technology from 0.5 µm down to 0.15 µm whereby it is now possible to define the primary distribution and also provide count information in the tail of pharmaceutical emulsions. In addition, by focusing the beam of detection to a fine point, particles can be sized and counted at concentrations up to 106 particles/mL. Presently, no other available technique can provide both sets of information. In this study, the focused beam system is used to count and size the primary distribution and large-diameter droplet tail of emulsions and determine their viability according to USP <729>.
Figure A shows a representative FX-Nano system histogram result of a TPN. Not only was the mean droplet size determined but also the large-diameter droplet tail.
Figure B shows a comparison of three TPNs with mean diameters of between 0.3-0.35 µm. From this data emulsion instability can be predicted. Sample LN clearly shows an increase in oversized particles due to coalescence.