Issue link: https://www.e-digitaleditions.com/i/1052795
Pharmaceutical Technology LABORATORY BEST PRACTICES 2018 33 tallized from light petroleum, producing needle-like crystals (Figure 4). When Upjohn acquired the distri- bution rights of this non-steroidal and anti-inflam- matory pain killer, the company developed a process using light alcohols. This newer process produced a solid form that is more free-flowing and with larger particle size in general and a more granular structure (Figure 5) (6). For this study on the effect of vortexing, needle-like crystals with an approximate aspect ratio of about 1:6 were sought. Therefore, a recrystallization of commer- cially available ibuprofen was performed from hexane. Measurement of particle size distribution Particle size measurement using laser diffraction was chosen to evaluate the impact of various vor- tex mixers. This technique was chosen because any changes to morphology would likely show up in the distribution, and it is a common technique for the measurement of particle-size distribution in this size range. A calibrated laser diffraction instrument was chosen to conduct the testing. The refractive index for ibuprofen was obtained from the instru- ment manual. The instrument stirrer settings and dispersant with detergent concentration were cho- sen based on a previous study (7) of method devel- opment of ibuprofen crystals using light scattering technique as noted in Table II. The remainder of the settings was chosen from laboratory best practices. To obtain a representative impact of various vortex mixers on sample preparation, a statistical design of experiments (DoE) was used. One of the vortex mixers was not included in the DoE as the intensity was not able to be varied, so only two of the vortex mixers were used. Particle size distribu- tions from the different morphologies of ibuprofen are shown in Figure 6. The responses measured during the particle size measurement DoE are given in Table III. The factors and ranges of each factor are given in Table IV and Figure 5: Irregular Ibuprofen. Figure 3: Shear of various vortex mixers. Figure 4: Acicular Ibuprofen. 6.0E-02 5.0E-02 4.0E-02 3.0E-02 2.0E-02 1.0E-02 0.0E+00 0 2 4 6 8 10 12 Shear (Pa) Vortex Mixer Setting Shear Generated by Vortex Mixers Vortexer Type 1 (VORT-189) Vortexer Type 2 (VORT-17) Vortexer Type 1 (VORT-34)