Polymorphism can influence every aspect of the properties of a solid including the shelf life, dissolution rate, solubility, formulation properties and processing properties of a solid drug. A deeper understanding of polymorphism and related solid state properties would ensure an improved quality of the materials used throughout drug preparation, dosage form formulation and clinical trials. Therefore, determination of the existence of polymorphs and pseudopolymorphs, characterization of different solid state forms and their respective properties, and controlling the existing form in the resulting formulation all form part of a rapidly growing field within pharmaceutical research and industry. Carbamazepine (CBZ) was the model drug used in this study. FT-Raman spectroscopy was chosen as a main investigative technique in this study to evaluate its potential in monitoring (pseudo)polymorphic conversions in aqueous suspensions in the absence or presence of various pharmaceutical excipients. Partial least squares analysis (PLS) was used for quantitative analysis of the spectral data. Earlier it has been found that CBZ converts rapidly to the dihydrate (DH) when exposed to humidity or water, and this has been reported to be the main reason for the sometimes observed greatly decreased bioavailability of marketed CBZ tablets. In this study, the conversion kinetics of CBZ (forms I, II and III) to DH in aqueous suspension were found to be first order kinetics with an unconverted portion (R� [greater than or equal to] 0.95), where the crystal morphology appeared to play a more important role in its conversion kinetics than the polymorphic form. The influence of pharmaceutical excipients on the conversion of CBZ in aqueous suspension was also explored. For excipients such as methylcellulose (MC), hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) which have both a low solubility parameter (< 27.0 MPa[1/2]) and strong hydrogen bonding groups, complete inhibition of the conversion of CBZ was possible even at a very low concentration (0.1 % w/v). Raman spectroscopy showed its high applicability in investigating CBZ conversion kinetics and screening of excipient effects in aqueous environment. It was demonstrated that Raman has a robust nature in quantitative analysis since problems such as different particle size, morphology, and spatial distribution of the two solid state forms of the drug seemed not to have significant influence on Raman scattering. This study has also clarified the relative importance of many contributing factors (type of crystalline form (CBZ or DH), crystal morphology, surface area, and excipient interactions with drug particles) influencing the in vitro dissolution of CBZ. The solid state characterization approach taken in this study will provide a deeper insight into the dissolution performance of drugs and should thus lead to a better understanding of in vitro/in vivo behavior of drugs.

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Thesis (M.S.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains ix, 110 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 54-59).

Reproduction de : Thèse de doctorat : Génie des procédés et de l'environnement : Toulouse, INPT : 2007. / Titre provenant de l'écran-titre. Bibliogr. 93 réf.

Thèse de doctorat : Sciences de l'univers et de l'environnement. Physique des aérosols : Paris 12 : 2007. / Titre provenant de l'écran-titre. Bibliogr. : 216 réf.

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The objective of this Thesis is to devise a system for the "rheology-based design" of non-settling (homogeneous) slurry pipelines that is more conducive to application by practicing engineers without impairing its accuracy or utility for research purposes. The cornerstone is the development of a new rheological model and constitutive equation for homogeneous slurry based on the aggregation/deaggregation of the suspended mineral particles. This “yield plastic” model is shown to describe a family of models that includes the Newtonian, Bingham plastic and Casson models as special cases. It also closely approximates the results of many consistency models, including power law, yield power law, Cross and Carreau-Yasuda. The yield plastic model is then used to develop design equations to determine the pressure-gradient of laminar and turbulent pipe flow. A relative energy dissipation criterion is proposed for the laminar-turbulent transition and shown to be consistent with currently used transition models for Newtonian and Bingham fluids. Finally, a new dimensionless group (the “stress number”) is proposed that is directly proportional to the pressure-gradient and independent of the velocity. When the design equations are presented graphically in terms of the stress number and the plastic Reynolds number, the resulting “design curve diagram” is shown to be a dimensionless (pressure-gradient vs. velocity) pipe flow curve. The net result is that the hydraulic design of homogeneous slurry systems only requires the use of a single constitutive equation and three engineering design equations. The results are presented in a conceptually easy form that will foster an intuitive understanding of non-Newtonian pipe flow. This will assist engineers to understand the impact of slurry rheology when designing, operating and troubleshooting slurry pipelines and, in the future, other slurry related processes.

The possible benefits of employing inerters in automotive suspensions are explored for passenger comfort and handling. Different suspension strut designs in terms of the relative arrangement of springs, dampers and inerters have been considered and their performance compared with that of a conventional system. An alternate method of electrically realizing complex mechanical circuits by using a linear motor (or a rotary motor with an appropriate mechanism) and a shunt circuit is then proposed and evaluated for performance. However, the performance improvement is shown from simulations to be significant only for very stiff suspensions, unlike those in passenger vehicles. Hence, the concept is not taken up for prototyping. Variable damping can be implemented in suspension systems in various ways, for example, using magneto-rheological (MR) fluids, proportional valves, or variable shunt resistance with a linear electromagnetic motor. Hence for a generic variable damping system, a control algorithm is developed which can provide more comfort and better handling simultaneously compared to a passive system. After establishing through simulations that the proposed adaptive control algorithm can demonstrate a performance better than some controllers in prior-art, it is implemented on an actual vehicle (Cadillac STS) which is equipped with MR dampers and several sensors. In order to maintain the controller economical so that it is practically viable, an estimator is developed for variables which require expensive sensors to measure. The characteristic of the MR damper installed in the vehicle is obtained through tests as a 3-dimensional map relating suspension speed, input current and damping force and then used as a look-up table in the controller. Experiments to compare the performance of different controllers are carried out on smooth and rough roads and over speed bumps.

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