Development of an experiment-based robust design paradigm for multiple quality characteristics using physical programming

The well-known quality improvement methodology, robust design, is a powerful and cost-effective technique for building quality into the design of products and processes. Although several approaches to robust design have been proposed in the literature, little attention has been given to the development of a flexible robust design model. Specifically, flexibility is needed in order to consider multiple quality characteristics simultaneously, just as customers do when judging products, and to capture design preferences with a reasonable degree of accuracy. Physical programming, a relatively new optimization technique, is an effective tool that can be used to transform design preferences into specific weighted objectives. In this paper, we extend the basic concept of physical programming to robust design by establishing the links of experimental design and response surface methodology to address designers’ preferences in a multiresponse robust design paradigm. A numerical example is used to show the proposed procedure and the results obtained are validated through a sensitivity study

Formulating effective performance measures for systems with multiple quality characteristics

Thesis (S.M.)--Massachusetts Institute of Technology, System Design & Management Program, 1999.Includes bibliographical references (leaves 69-71).by Ebad Jahangir.S.M

RESEARCH AND DEVELOPMENT EFFORT IN DEVELOPING THE OPTIMAL FORMULATIONS FOR NEW TABLET DRUGS

Seeking the optimal pharmaceutical formulation is considered one of the most critical research components during the drug development stage. It is also an R&D effort incorporating design of experiments and optimization techniques, prior to scaling up a manufacturing process, to determine the optimal settings of ingredients so that the desirable performance of related pharmaceutical quality characteristics (QCs) specified by the Food and Drug Administration (FDA) can be achieved. It is widely believed that process scale-up potentially results in changes in ingredients and other pharmaceutical manufacturing aspects, including site, equipment, batch size and process, with the purpose of satisfying the clinical and market demand. Nevertheless, there has not been any single comprehensive research work on how to model and optimize the pharmaceutical formulation when scale-up changes occur. Based upon the FDA guidance, the documentation tests for scale-up changes generally include dissolution comparisons and bioequivalence studies. Hence, this research proposes optimization models to ensure the equivalent performance in terms of dissolution and bioequivalence for the pre-change and post-change formulations by extending the existing knowledge of formulation optimization. First, drug professionals traditionally consider the mean of a QC only; however, the variability of the QC of interest is essential because large variability may result in unpredictable safety and efficacy issues. In order to simultaneously take into account the mean and variability of the QC, the Taguchi quality loss concept is applied to the optimization procedure. Second, the standard 2×2 crossover design, which is extensively conducted to evaluate bioequivalence, is incorporated into the ordinary experimental scheme so as to investigate the functional relationships between the characteristics relevant to bioequivalence and ingredient amounts. Third, as many associated FDA and United States Pharmacopeia regulations as possible, regarding formulation characteristics, such as disintegration, uniformity, friability, hardness, and stability, are included as constraints in the proposed optimization models to enable the QCs to satisfy all the related requirements in an efficient manner. Fourth, when dealing with multiple characteristics to be optimized, the desirability function (DF) approach is frequently incorporated into the optimization. Although the weight-based overall DF is usually treated as an objective function to be maximized, this approach has a potential shortcoming: the optimal solutions are extremely sensitive to the weights assigned and these weights are subjective in nature. Moreover, since the existing DF methods consider mean responses only, variability is not captured despite the fact that individuals may differ widely in their responses to a drug. Therefore, in order to overcome these limitations when applying the DF method to a formulation optimization problem, a priority-based goal programming scheme is proposed that incorporates modified DF approaches to account for variability. The successful completion of this research will establish a theoretically sound foundation and statistically rigorous base for the optimal pharmaceutical formulation without loss of generality. It is believed that the results from this research will have the potential to impact a wide range of tasks in the pharmaceutical manufacturing industry

Experimental Studies on Machinability of Inconel Super Alloy during Electro-Discharge Machining: Emphasis on Surface Integrity and Metallurgical Characteristics of the EDMed Work Surface

Inconel alloys are Nickel-Chromium based high temperature super alloys widely applied in aerospace, marine, nuclear power generation; chemical, petrochemical and process industries. Execution of traditional machining operations on Inconel super alloy is quite difficult due to its very low thermal conductivity which increases thermal effects during machining operations. Inconel often exhibits strong work hardening behavior, high adhesion characteristics onto the tool face, and thereby alters cutting process parameters to a remarkable extent. Additionally, Inconel may contain hard abrasive particles and carbides that create excessive tool wear; and, hence, surface integrity of the end product appears disappointing. The extent of tool life is substantially reduced. Thus, Inconel super alloys are included in the category of ‘difficult-to-cut’ materials. In view of the difficulties faced during conventional machining, non-traditional machining routes like Electro-Discharge Machining (EDM), Wire Electro-Discharge Machining (WEDM), micro-machining (micro-electro-discharge drilling) etc. are being attempted for processing of Inconel in order to achieve desired contour and intricate geometry of the end product with reasonably good dimensional accuracy. However, low material removal rate and inferior surface integrity seem to be a challenge. In this context, the present dissertation has aimed at investigating machining and machinability aspects of Inconel super alloys (different grades) during electro-discharge machining. Effects of process control parameters (viz. peak discharge current, pulse-on time, gap voltage, duty factor, and flushing pressure) on influencing EDM performance in terms of Material Removal Rate (MRR), Electrode Wear Rate (EWR) and Surface Roughness (SR) of the EDMed Inconel specimens have been examined. Morphology along with topographical features of the EDMed Inconel work surface have been studied in view of severity of surface cracking and extent of white layer depth. Additionally, X-Ray Diffraction (XRD) analysis has been carried out to study metallurgical characteristics of the EDMed work surface of Inconel specimens (viz. phases present and precipitates, extent of grain refinement, crystallite size, and dislocation density etc.) in comparison with that of ‘as received’ parent material. Results, obtained thereof, have been interpreted with relevance to Energy Dispersive X-ray Spectroscopy (EDS) analysis, residual stress and micro-indentation hardness test data. Effort has been made to determine the most appropriate EDM parameters setting to optimize MRR, EWR, along with Ra (roughness average), relative Surface Crack Density (SCD), as well as relative White Layer Thickness (WLT) observed onto the EDMed work surface of Inconel specimens. Moreover, an attempt has been made to examine the ease of electro-discharge machining on Inconel work materials using Deep Cryogenically Treated (DCT) tool/workpiece. A unified attempt has also made to compare surface integrity and metallurgical characteristics of the EDMed Inconel work surface as compared to the EDMed A2 tool steel (SAE 304SS) as well as EDMed Titanium alloy (Ti-6Al-4V)