Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2011. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Melt extrusion is an alternative processing technique that operates continuously, reduces the total number of unit operations, allows for incorporation of difficult-to-process drug substances, and has the potential to achieve tablets of better quality and consistency compared to traditional methods. Thus, our goal was to evaluate melt extrusion as a viable processing alternative and expand our scientific knowledge such that we gain predictive capabilities of tablet characteristics, i.e., quality by design. This new knowledge will aid future process design thereby helping to reduce time and costs associated with pharmaceutical solid dosage form production. The residence time distribution for melt extrusion has been characterized using a single parameter model. When combined with assumed first-order reaction rate kinetics and an Arrhenius reaction rate constant, the model can accurately predict the amount of drug product lost to temperature driven degradation. The model prediction agreed well with experimentally determined fractional conversion. The physical stability of amorphous Molecule A was characterized using enthalpy of relaxation measurements. Molecular level rearrangements are the source of physical instability for the fragile glass forming Molecule A. The instability can be modified by introducing a second component, which contributes to the overall enthalpy change. Coating amorphous Molecule A tablets with a polyvinyl alcohol based coating material reduces moisture uptake during storage. The coating material preferentially uptakes water from the atmosphere, restricting moisture from entering the tablet core and causing premature dissolution or degradation. The dissolution behavior of Molecule A tablets can be tailored with the addition of water soluble materials. Dissolution rate constants for Molecule A tablets have been calculated for different formulations and can be used as a resource when designing new solid dosage forms with desired dissolution characteristics. A novel 100% Molecule A melt extrusion process has been created, reducing the number of overall unit operations and eliminating troublesome blending inconsistencies. An additional formulation that maintains the crystallinity of Molecule A by processing with polyethylene glycol below Molecule A's melting temperature is physically and chemically stable and ready for implementation in a continuous production line. The mixing achieved within the extruder for this formulation is sufficient to eliminate a pre-mixing unit operation. / by Erin R. Bell. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1974. / Vita. / Bibliography: leaves 343-354. / by Ayodeji Jeje. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2000. / Includes bibliographical references. / Traditional approaches in Model Predictive Control (MPC) suffer from several weaknesses such as: (a) Satisfying the output constraints over a finite control horizon and guaranteeing closed loop stability. (b) The need for infinite horizon for robust stability and performance. (c) Limited representation of plant-model mismatch. (d) Inability to shape frequency response characteristics of the outputs through systematically selected weights in the objective function. (e) Significant numerical complexity which depends on the number of input constraints. These weaknesses are addressed by formulating and solving the MPC in a multiscale (time/scale) domain. Based on the wavelet transformation of time domain models, the multiscale models are defined on dyadic or higher-order trees, whose nodes are used to index the values of any variable, localized in both time and scale (range of frequencies). The objective function, state equations, output equations and constraints on inputs and outputs are transformed into the multiscale domain. Moreover, feedback information is also generated for all scales using a multiscale constrained state estimator, providing rich depiction of the plant-model mismatch (including modeling errors, external disturbances and measurement noise) than the pure time domain formulation. This problem formulation: (i) incorporates rich depiction of feedback errors and provides an environment to identify plant-model mismatch at multiple scales, (ii) it provides a natural framework for optimum fusion of multirate measurements and control actions. The solution to this problem, (i) satisfies all the constraints on inputs and outputs if the problem is feasible at least over an infinite horizon and (ii) satisfies the frequency response specifications on the controlled outputs. In addition it reduces the computational load through two very effective mechanisms. (l) Sets horizon to the required length at each open loop optimization step. (2) It minimizes the search space for active constraints, because once a constraint is determined to be active at a scale, all the lower scale depictions of the constraint emanating from that node, will also be active, and can be solved using parallelized algorithms thus reducing the complexity further and allowing handling of larger problems with more constraints. / by Orhan I. Karslıgil. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1983. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE / Bibliography: leaves 164-170. / by Edward Carl Hume, III. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2001. / Includes bibliographical references. / Historically, using suitable mechanical replacements for bone has been a priority in designing permanent, load-bearing orthopedic implants. As a result, the biomaterials used in these implants have been largely limited to bioinert titanium-based alloys, as well as to polycrystalline alumina and zirconia ceramics. However, analysis of implants incorporating these traditional biomaterials indicated that most failures involved an unstable implant-tissue interface and/or a mismatch of the mechanical behavior of the implant with the surrounding tissues. As a result, up to 20% of patients receiving permanent, load-bearing implants may undergo a revision operation. The objective of this research was to develop an alternative biomaterial that combined both mechanical resilience and an osteoconductive surface to provide a stable interface with the surrounding connective tissue so that the need for revision operations may be significantly reduced. In the effort to address the issue of mechanical strength and bioactivity simultaneously, hydroxyapatite (HAP) has generated considerable interest. Though a commonly used bioceramic, HAP has been limited by its processability. This material is sensitive to non-stoichiometry and impurities during synthesis and processing due to its complex composition and crystal structure (Ca10(P04)6(OH)2, P63/m). / (cont.) Consequently, conventionally processed HAP materials lack phase purity and homogeneity. Densification of HAP requires high temperatures that result in grain growth and decomposition into undesired phases with poor mechanical and chemical stability. To circumvent densification at high temperatures, glassy additives have been introduced to promote liquid-phase sintering at a lower temperature. However, the presence of a secondary glassy phase gave rise to poor mechanical characteristics. Hence, clinical applications of HAP have been limited to powders, coatings, porous bodies, and non-load-bearing implants. To overcome the deficiencies of conventionally processed HAP, nanostructure processing was applied, which allowed for materials design from the molecular level. By using an aqueous chemical precipitation technique, a fully dense, transparent, nanostructured HAP-based bioceramic that exhibited superior mechanical properties and enhanced tissue bonding was obtained. Processing parameters affecting the molecular and structural development of HAP were used to tailor HAP stoichiometry, crystallite size, morphology and surface chemistry for optimal thermal stability and sinterability. Unlike conventionally processed HAP, the stoichiometric, equiaxed, nanocrystalline HAP powders demonstrated significantly enhanced sinterability by fully densifying at a remarkably low temperature of 900ʻC with pressure-assisted sintering. / (cont.) Furthermore, high-resolution electron micrographs illustrated that the sintered compact possessed a uniform and ultrafine microstructure with an average grain size of -100 nm, with no glassy or amorphous interfaces along the grain boundaries. The crystallinity of the HAP grains and grain boundaries and the minimal flaw sizes could be credited for the superior strength of nanostructured HAP compared to conventional HAP. Compared to polycrystalline HAP, nanocrystalline HAP also provided greater osteoblast function. In vitro experiments indicated that nanocrystalline HAP surfaces enhanced cell attachment, proliferation and mineralization. The larger grain boundary volume resulting from the ultrafine microstructure might have enhanced protein adsorption, ... / by Edward Sun Ahn. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1994. / Includes bibliographical references. / by Paschalis Alexandridis. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, June 2005. / Includes bibliographical references. / Over the last decade, the sequential layer-by-layer assembly of oppositely charged polyelectrolytes has received much interest for the deposition of film architectures, ranging from tens to hundreds of nanometers in thickness, that can be precisely tuned as a function of the processing conditions. The resulting polyelectrolyte multilayer (PEM) constructs are being investigated as biomaterials, photonic structures, electrochemical devices, and separation membranes. There is a distinct lack of literature, however, on the friction-and-wear behavior of these nanocoatings, and their exploitation in systems with tribological problems of practical relevance. In addition, their mechanical properties, crucial for the success of almost all applications being studied, have not been systematically characterized. This thesis focuses on the elucidation of the tribological and mechanical properties of PEMs composed predominantly of weak polyelectrolytes--poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA). In general, the friction coefficients of PAH/PAA PEM-coated substrates were at least marginally higher than those exhibited by their uncoated counterparts, in the absence of substrate wear. The films, however, demonstrated a significant capacity for wear prevention of underlying substrates in the dry state, and also in the presence of bovine calf serum, used to simulate joint synovial fluid. In the latter case, a significant decrease in wear rates, in tests using a clinically relevant number of cycles and articulation pattern, pointed to the efficacy of PEM-coated systems for wear reduction in total joint replacement prostheses; wear particle- induced implant loosening remains a major cause of revision surgeries. / (cont.) To tune the frictional response of PEMs without compromising their wear-retarding behavior, various strategies were explored; these included surface capping with a block co-polymer, in-situ synthesis of silver nanoparticles in the films, and assembly of composites containing PAH and multi-wall carbon nanotubes. The engineered coatings find possible applications in microelectromechanical systems (MEMS) where friction, wear, and stiction can be detrimental to device performance. Nanoindentation was employed to probe the mechanical behavior of these ultra-thin films. It was demonstrated that the modulus and hardness of PAH/PAA PEMs could be tuned as a function of the pH of the polyelectrolyte solutions used for their assembly. The mechanical response of these structures was superior to either parent polyelectrolyte and also commercially used polymeric systems. The mechanical properties were studied at ambient conditions and in the presence of a liquid medium. / by Prem Venkatachalam Pavoor. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1994. / Includes bibliographical references (leaves 244-254). / by Maria Cláudia Ferreira Drumond de Sousa. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1992. / Vita. / Includes bibliographical references (leaves 879-885). / by David Leonard Wagger. / Ph.D.

Thesis (B.S.) Massachusetts Institute of Technology. Dept. of Chemical Engineering, 1950. / MIT copy bound with: Fermentation of molasses by the clostridium acetobutilycum / Luis Riva. 1950. / Bibliography: leaves 39-40. / by Vinson R. Simpson, Jr. / B.S.