Document Type


Date of Award

Summer 8-31-2015

Degree Name

Doctor of Philosophy in Chemical Engineering - (Ph.D.)


Chemical, Biological and Pharmaceutical Engineering

First Advisor

Piero M. Armenante

Second Advisor

Gerard Bredael

Third Advisor

Zongming Gao

Fourth Advisor

Costas G. Gogos

Fifth Advisor

Norman W. Loney

Sixth Advisor

Laurent Simon


Dissolution testing apparatuses and shaker flasks agitated by shaker tables are laboratory systems routinely found in many laboratories at most companies and agencies, and especially in pharmaceutical companies. These devices are commonly used in a number of applications, from drug development to quality control. Despite their common use, these systems have not been fully investigated from an engineering perspective in order to understand their operation characteristics. For example, the hydrodynamics of many of these systems have received little attention until relatively recently, and only over the last few years have some of these systems, such as the USP dissolution testing Apparatus 2, been studied in greater detail by a few research groups, including our group at NJIT. Meanwhile, a number of modifications have been introduced in industry to simplify the practical use of these devices and to automate many of the processes in which they are utilized. This, in turn, has resulted in the introduction of variability in the way these devices are operated, with possible implication for the results that they generate in laboratory experiments and tests.

Therefore, this work was aimed at studying some of these devices in order to quantify how such systems operate and what the implications for their use in the laboratory are. More specifically, the systems that were examined here included the USP Dissolution Testing Apparatus 2 with and without automatic sampling probes, dissolution testing mini vessel apparatuses, and baffled shaker flasks. In order to study all these phenomena, a number of tools were used, including Particle Image Velocimetry (PIV) and Computational Fluid Dynamics (CFD) to investigated the hydrodynamics of these systems; experimental tablet dissolutions under a number of controlled environments; and a combination of experimental, computational and modeling approaches to study mass transfer and solid suspension effects. The issues that were investigated depended on the specific apparatus.

For the case of the USP Dissolution Testing Apparatus 2, the effects of the presence of different probes on the hydrodynamics in the dissolution vessel and on the dissolution profiles using solid dosage forms were investigated in this work. The results indicate that in most cases, the presence of the probe resulted in statistically significant increases in the dissolution curves with respect to the curves obtained without the probe, and that tablets at, or close to, the center of the vessel were more significantly affected by the presence of the probe, and so were tablets located immediately downstream of the probe. The hydrodynamic effects generated by the arch-shaped fiber optic probe were small but clearly measurable. The changes in velocity profiles in the dissolution vessel resulted in detectable differences in the dissolution profiles, although not high enough to cause test failures. However, these differences could contribute to amplify the difference in dissolution profiles in those cases in which tablet has an intrinsically higher release rate. In addition, the minimum agitation speed, Njs, to achieve particle suspension was investigated. A novel method to determine Njs was first developed and then applied to determine Njs as a function of different operating variables.

Similarly, the hydrodynamics of smaller dissolution apparatuses termed “minivessels” were studied here and compared with the standard USP 2 system. The flow pattern in minivessels was obtained by both CFD simulations and PIV velocity measurements for four different agitation speeds in the mini vessel, and it was shown to result in flow patterns qualitatively similar to those in the standard USP 2 system. The velocity profiles were also compared on several iso-surfaces for the mini vessel system and the standard system, showing difference between two systems. In the most important zone, i.e., the inner core zone at the vessel bottom, the velocities were similar on the lowest iso-surface, especially for the axial velocity at 100rpm and 125rpm in the mini vessel compared with 100rpm in the 900mL USP 2 system. This was not clearly the case for iso-surfaces above the bottom zone.

Finally, the hydrodynamics of baffled shaker flask was investigated. These baffled “trypsinizing” flasks are similar to the typical Erlenmeyer-type conical shaker flasks commonly used in biological laboratories but with a major difference, in that they are provided with vertical indentations in the glass flask so as to create vertical baffles that promote better mixing when shaken. Measurements of the velocity in the flask were obtained using PIV for seven rotation speeds of 100, 125, 150, 160, 170, 200, and 250 rpm. Two vertical cross sections were measured to obtain the velocity profiles in the flask: the one with largest diameter of the flask, and the one with the smallest diameter. The 1D energy spectra indicate nearly isotropic flow in the BF for all rotation speeds and the existence of inertial subrange, which validate the use of dimensional argument analysis for the estimation of energy dissipation rate.

The results obtained in this work will contribute to increase our understanding of the performance of a number of very common and important laboratory apparatus thus contributing to a more appropriate use of all these devices in both industry and federal and state agencies.



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