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34 Pharmaceutical Technology LABORATORY BEST PRACTICES 2018 P h a r mTe c h . c o m were used to generate the possible DoE matrices. The factors were entered into a commercial statis- tics software package, and a full factorial design was chosen as the base design. Discussion with the chemist and development results suggested the vortexer level was most likely non-linear, thus, the full factorial design was augmented with a single curvature term, vortexer level*vortexer level. A commercial statistics software package was used to generate a randomized testing matrix that was followed by the chemist. DoE results The correlation coefficients are given below in Table V. In general, an R 2 > 0.8, 0.9, or even 0.95, depending on the system, application, and acceptable confi- dence level, is considered to be an acceptable fit. The commercial statistics software package re- ports each factor in the effect tests section along with its corresponding probability greater than the F statistic (Prob>F) as shown in Tables VI–VIII. In practice, factors whose Prob>F are ≤ 0.05 are considered statistically significant at the 95% con- fidence level. Discussion Vortexer equivalency. The vortexers appear to have similar shear outputs at some settings; however, they clearly are not equivalent between settings 4 through 8. When using methods that require gentle vortexing or when transferring methods between laboratories, this difference can be the cause of various errors when performing par- ticle size distribution measurements of pharma- ceuticals. Effect on particle size distribution. Preliminary de- velopment work suggested the vortexer level was non-linear; hence the addition of the curvature term in the regression model. Sample Preparation Figure 6: Particle size distributions of varying ibuprofen morphologies. 7 6 5 4 3 2 1 0 0.01 0.1 1 10 100 1000 10000 Particle Size (μm) Acicular Ibuprofen Irregular Ibuprofen Differential Size Distribution (%) Table II: Analysis settings. Instrument parameter Setting Refractive index 1.52 Absorption index 0.01 Stirrer speed (rpm) 2000 Obscuration (%) 5-20 Dispersant concentration (%w/v) 0.1% Triton X100 in 18 mΩ purified water Table III: Responses measured during the particle size measurement design of experiment. Particle Size (μm) D[v,0.1] D[v,0.5] D[v,0.9] Table IV: Factors and ranges. Factors Range Minimum Maximum Vortexer level 3 7 Vortexer duration (s) 0 60 Vortexer Type I Type II Morphology Acicular Irregular Table V: Correlation coefficients. Response Correlation coefficient D[v,0.1] 0.98 D[v,0.5] 0.91 D[v,0.9] 0.95