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Particle Size Evaluation
Mark G. Klang, MS, RPh, BCNSP, PhD
Core Manager, Research Pharmacy
Memorial Sloan Kettering Cancer Center
New York, New York
Particle size is a significant aspect of pharmaceutical development. For a poorly soluble drug, dissolution is the rate-limiting step toward absorption. Reducing the particle size will increase the surface area, improve dissolution, and enhance bioavailability.1
A disparity in particle size and density will allow powders to separate when placed in a centrifugal blender. Creating a uniformity of particle size allows for a homogeneous mixture.2 Dynamic light scattering (DLS) is an effective measure of particles in a powder system, but should not be used for evaluation of particle-size limits in an injectable medication. DLS is an effective tool in the evaluation of powders as shown in United States Pharmacopeia (USP) Chapter <851>.3
An increase in the presence of particles greater than 5 mcm in an intravenous admixture will accumulate in pulmonary arterioles.4 In one hospital, the precipitate of calcium and phosphorus in a nutrition solution resulted in two patients' death and two others developing pulmonary complications.5 An evaluation of the potential for calcium/phosphate precipitate potential could have alerted the institution of the need for in-line filters. USP Chapter <788> allows for either microscopy (Method 1) or light obscuration (Method 2) to evaluate the number of particles greater than 10 mcm and 25 mcm.3
The extent of lipid particles in an intravenous emulsion is a measure of the stability as a reflection of the aggregation of oil droplets.6 When nutritional lipids are combined with dextrose, amino acids, and electrolytes, the resultant admixture is susceptible to destabilization of the emulsion. The point at which this aggregation becomes critical is identified by the volume weighted percent of particles greater than 5 microns (PFAT5). USP Chapter <729> allows the use of light scattering to determine the mean particle size of the smaller droplets, but requires light obscuration for the evaluation of PFAT5.3
The number and size of particles could be a measure of the effectiveness of a cleanroom to maintain aseptic environment.7 These counts reflect the capacity of the air filtration units to clear the viable and non-viable particulates generated by work done within the cleanroom.8 USP Chapter <797> addresses the evaluation of viable and non-viable particles within a cleanroom.3
In each of these cases different technologies are used for evaluation. Although some technologies can deliver a particle count, they may not be valid for that system. Always check with the USP for guidance on the appropriate testing methods.
References
- Hadziabdic J, Elezovic A, Rahic O et al. Stability of suspensions: Theoretical and practical considerations before compounding. IJPC 2015; 19(1): 78-85.
- Allen LV Jr. The basics of compounding powders and granules. IJPC 2001; 7(1): 36-39.
- United States Pharmacopeial Convention, Inc. United States Pharmacopeia 38-National Formulary 33. Rockville, MD: US Pharmacopeial Convention, Inc.; 2014: 504-506, 550-553, 583-585, 641-649.
- Allen LV Jr. Particulates in parenterals. IJPC 2000; 4(1): 43.
- Hill SE, Heldman LS, Goo ED et al. Fatal microvascular pulmonary emboli from precipitation of a total nutrient admixture solution. JPEN 1996; 20(1): 81-87.
- Driscoll DF, Thoma A, Franke R et al. Lipid globule size in total nutrient admixtures prepared in three-chamber plastic bags. Am J Health Syst Pharm 2009; 66(7): 649-656.
- Kastango ES, Douglass K. Quality assurance for sterile products. IJPC 2001; 5(4): 246-262.
- Eaton T, Wardle C, Whyte W. Use of a real-time microbial air sampler for operational cleanroom monitoring. PDA J Pharm Sci Tech 2014; 68(2): 172-184.
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