CFD modeling of pharmaceutical isolators with experimental verification of airflow.

Computational fluid dynamics (CFD) models have been developed to predict the airflow in a transfer isolator using a commercial CFD code. In order to assess the ability of the CFD approach in predicting the flow inside an isolator, hot wire anemometry measurements and a novel experimental flow visualization technique consisting of helium-filled glycerin bubbles were used. The results obtained have been shown to agree well with the experiments and show that CFD can be used to model barrier systems and isolators with practical fidelity. This indicates that CFD can and should be used to support the design, testing, and operation of barrier systems and isolators.

The nonsteady state modeling of freeze drying: in-process product temperature and moisture content mapping and pharmaceutical product quality applications.

INTRODUCTION: Theoretical models of the freeze-drying process are potentially useful to guide the design of a freeze-drying process as well as to obtain information not readily accessible by direct experimentation, such as moisture distribution and glass transition temperature, Tg, within a vial during processing. Previous models were either restricted to the steady state and/or to one-dimensional problems. While such models are useful, the restrictions seriously limit applications of the theory. An earlier work from these laboratories presented a nonsteady state, two-dimensional model (which becomes a three-dimensional model with an axis of symmetry) of sublimation and desorption that is quite versatile and allows the user to investigate a wide variety of heat and mass transfer problems in both primary and secondary drying. The earlier treatment focused on the mathematical details of the finite element formulation of the problem and on validation of the calculations. The objective of the current study is to provide the physical rational for the choice of boundary conditions, to validate the model by comparison of calculated results with experimental data, and to discuss several representative pharmaceutical applications. To validate the model and evaluate its utility in studying distribution of moisture and glass transition temperature in a representative product, calculations for a sucrose-based formulation were performed, and selected results were compared with experimental data. THEORETICAL MODEL: The model is based on a set of coupled differential equations resulting from constraints imposed by conservation of energy and mass, where numerical results are obtained using finite element analysis. Use of the model proceeds via a "modular software package" supported by Technalysis Inc. (Passage/ Freeze Drying). This package allows the user to define the problem by inputing shelf temperature, chamber pressure, container properties, product properties, and numerical analysis parameters required for the finite element analysis. Most input data are either available in the literature or may be easily estimated. Product resistance to water vapor flow, mass transfer coefficients describing secondary drying, and container heat transfer coefficients must normally be measured. Each element (i.e., each small subsystem of the product) may be assigned different values of product resistance to accurately describe the nonlinear resistance behavior often shown by real products. During primary drying, the chamber pressure and shelf temperature may be varied in steps. During secondary drying, the change in gas composition from pure water to mostly inert gas is calculated by the model from the instantaneous water vapor flux and the input pumping capacity of the freeze dryer. RESULTS: Comparison of the theoretical results with the experiment data for a 3% sucrose formulation is generally satisfactory. Primary drying times agree within two hours, and the product temperature vs. time curves in primary drying agree within about +/-1 degrees C. The residual moisture vs. time curve is predicted by the theory within the likely experimental error, and the lack of large variation in moisture within the vial (i.e., top vs. side vs. bottom) is also correctly predicted by theory. The theoretical calculations also provide the time variation of "Tg-T" during both primary and secondary drying, where T is product temperature and Tg is the glass transition temperature of the product phase. The calculations demonstrate that with a secondary drying protocol using a rapid ramp of shelf temperature, the product temperature does rise above Tg during early secondary drying, perhaps being a factor in the phenomenon known as "cake shrinkage." CONCLUSION: The theoretical results of in-process product temperature, primary drying time, and moisture content mapping and history are consistent with the experimental results, suggesting the theoretical model should be useful in process development and "trouble-shooting" applications.

Stress analysis of bone modeling response to rat molar orthodontics.

The purpose of this project was to determine if alveolar bone modeling could be associated with altered mechanical environment. Finite element stress analysis of an orthodontically tipped rat molar periodontium was performed. The distributions of mechanical components within the periodontal ligament and cortical bone were compared to the well-documented bone formation and resorption patterns in the alveolus of the tooth. It was concluded that in orthodontically induced bone modeling activity, locations of osteogenesis uniquely coincided with increased tension within the periodontal ligament, while bone resorption areas could be associated with increases in other components (minimum principal and maximum shear stresses, strain energy density, and von Mises) within the bone itself.

Mechanical simulation of the human mandible with and without an endosseous implant.

Clinical research has demonstrated that a high remodelling rate for cortical bone exists around a rigid endosseous implant. This phenomenon may be regulated by change in the mechanical environment. 3D finite element models of the human mandible with and without an endosseous implant have been created to investigate the mechanical environment adjacent to the left retromolar area where the ipsilateral implant was located. A bite force of 100 N was applied in the left premolar region. The mechanical environment before and after implantation were computed. The environment was characterized by the following parameters: the principal stresses, dilatational stress, and von Mises stress. The changes in these parameters due to the implantation were calculated. The results showed that the mechanical environment adjacent to the implant changed drastically due to the implant. The major changes in the mechanical parameters occurred adjacent to the bone-implant interface at the bony surface. The changes of the distribution of the mechanical parameters due to implantation were different. Implantation effects were local, and did not alter the overall mechanical environment.

Effect of a resilient layer in a removable partial denture base on stress distribution to the mandible.

The results of two-dimensional finite element analyses of a mandible indicate that a resilient layer within a denture base can act as an effective "shock absorber" and may slow down ridge resorption. Finite element models of similar types can easily be used to further investigate various applications of resilient layers. The magnitudes and distributions of stresses generated in the mandible by force application to two types of a distal extension denture base were determined and compared. The results were obtained by using the finite element method of stress analysis. In the first analysis, a conventional distal extension denture base resting on the mandible was simulated. In the second analysis, the same testing force was applied to a distal extension denture base with a resilient layer between the teeth and the basal seat. The results indicated that the stress distribution was more uniform during occlusal loading through a resilient layer. The vertical displacement of the alveolar ridge under the denture base with a resilient layer was far less than that of the conventional denture base.