Browsing by Author "Zhang, Feng"
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Item Identifying nonlinear variaiton patterns in multivariate manufacturing processes(Texas A&M University, 2005-02-17) Zhang, FengThis dissertation develops a set of nonlinear variation pattern identification methods that are intended to aid in diagnosing the root causes of product variability in complex manufacturing processes, in which large amounts of high dimensional in-process measurement data are collected for quality control purposes. First, a nonlinear variation pattern model is presented to generically represent a single nonlinear variation pattern that results from a single underlying root cause, the nature of which is unknown a priori. We propose a modified version of a principal curve estimation algorithm for identifying the variation pattern. Principal curve analysis is a nonlinear generalization of principal components analysis (PCA) that lends itself well to interpretation and also has theoretically rich underpinnings. The principal curve modification involves a dimensionality reduction step that is intended to improve estimation accuracy by reducing noise and improving the robustness of the algorithm with the high-dimensional data typically encountered in manufacturing. An effective visualization technique is also developed to help interpret the identified nonlinear variation pattern and aid in root cause identification and elimination. To further improve estimation robustness and accuracy and reduce computational expense, we propose a local PCA based polygonal line algorithm to identify the nonlinear patterns. We also develop an approach for separating and identifying the effects of multiple nonlinear variation patterns that are present simultaneously in the measurement data. This approach utilizes higher order cumulants and pairwise distance based clustering to separate the patterns and borrows from techniques that are used in linear blind source separation. With the groundwork laid for a versatile flexible and powerful nonlinear variation pattern modeling and identification framework, applications in autobody assembly and stamping processes are investigated. The pattern identification algorithms, together with the proposed visualization approach, provides an effective tool to aid in understanding the nature of the root causes of variation that affect a manufacturing process.Item Importance of stability of pharmaceutical formulations(2016-12) Hengsawas, Soraya; Williams, Robert O., 1956-; Cui, Zhengrong; Frei, Christopher R; Zhang, Feng; McGinity, James WStability is an essential quality attribute for pharmaceutical formulations. Evaluation of drug stability can prevent toxicity and increase safety, efficacy and quality of the final drug product. In this work, various factors affecting stability of both small molecule and biopharmaceutical compounds were investigated. In the first study, we initially hypothesized that albendazole, a poorly water soluble drug, could be prepared by melt extrusion to enhance its dissolution and bioavailability. However, it was found that albendazole was severely degraded by heat and shear during extrusion. When combined with methanesulfonic acid and Kollidon VA 64, amorphous albendazole solid dispersion was successfully prepared by an alternative process, spray drying, to enhance dissolution and shelf-stability. In the second study, the stability of a caveolin-1 scaffolding domain (CSP7), which is a newly developed peptide for the treatment of idiopathic pulmonary fibrosis, was investigated in order to achieve an optimal formulation for in vivo clinical studies. This study showed the physical instability of the peptide, which was aggregation induced by moisture, and the crystallization of bulking agent on its stabilizing effect. It was found that the moisture-induced aggregates were reversible and could be prevented by pH adjustment and incorporation of lactose in the composition. Lactose, a reducing sugar, stabilized the peptide possibly as a result of chemical interactions with CSP7 (e.g., formation of a Schiff base with the N-terminal amino group of CSP7). Based on these results, lactose stabilized CSP7 against moisture-induced aggregation in the solid state to a greater degree than mannitol. Additionally, stability of the CSP7-bulking agent formulations was not affected by nebulization using vibrating mesh nebulizers. Lastly, the effect of nebulization using vibrating mesh nebulizers on stability of tissue-type plasminogen activator (tPA) and single-chain urokinase plasminogen activator (scuPA), being studied for the treatment of inhalational smoke-induced acute lung injury (ISALI), was evaluated. For scuPA, the effect of lyophilization on its stability was also studied. The results showed that scuPA was stable after lyophilization (scuPA) and that both proteins were stable following reconstitution and nebulization. There were only slightly differences between the active and passive vibrating mesh nebulizers. In conclusion, from our work, the physical and chemical stability of small- and macromolecules was affected by formulation composition, processing and post-processing factors.Item Scattering Properties of Oriented Hexagonal Ice Crystals(2010-01-14) Zhang, FengTo interpret the data from spaceborn lidar measurements, one must have a basic understanding of the backscattering of oriented ice particles. The conventional raytracing method is not applicable to the scattering of light by oriented particles. In this study, the dipole approximation (DDA) method is employed to the scattering of light on oriented hexagonal ice columns and plates with various tilting angles. It is found that the oriented hexagonal ice particles tend to have strong backscattering intensity with low depolarization ratios which are strongly dependant on the tilting angle of oriented particles. The present results show that the e ffect of particle orientation plays an important role in determining the optical properties of ice clouds consisting of horizontally oriented ice crystals.Item Thermal processing cyclodextrins and thermoplastic polymers for bioavailability enhancement of poorly water-soluble drugs(2014-05) Bennett, Ryan Cole; Williams, Robert O., 1956-; McGinity, James W.; Smyth, Hugh D; Whitman, Christian P; Zhang, FengWith the advent and utility of high throughput screening, the number of drug substances in the developmental pipeline of pharmaceutical industries that are poorly water-soluble has increased dramatically. The rate of drug absorption from the particular dosage form is controlled by the drug solubility and dissolution rate in the biological fluids at the absorption site. Amorphous solid dispersions have emerged as products that may increase the level of drug supersaturation while also maintaining levels for extended periods of time. Thermal processing techniques have become commonly used to produce amorphous dispersions of carrier and dissolved drug in order to improve aqueous solubility. Within this dissertation, two thermal processes were investigated for the preparation of solid dispersions: hot-melt extrusion (HME) and KinetiSol Dispersing® (KSD). In addition, this dissertation evaluates the ability of cyclodextrin and thermoplastic polymers following thermal processing to enhance the solubility and stabilize an amorphous drug form in solution. HME has become a widely reported processing technique to prepare dispersion products. However the process exudes a number of limitations that prevent the successful formulation of many poorly-water soluble drug substances. In the first study, the novel fusion-based processing technique, KSD, was utilized to prepare an amorphous solid dispersion containing a poorly water-soluble gum extract exhibiting oncological indication. Because the latter entity could not be prepared by HME to yield amorphous and fully potent drug dispersions, KSD was applied as a suitable processing technology for rendering a high melting point substance amorphous in thermoplastic polymers. In comparison to a marketed product, the KSD-processed amorphous dispersions enhanced dissolution performance and resulting biovailability in an in vivo study. In the second study, combinations of hydrophilic and enteric polymers were processed by HME to enhance and extend the levels of supersaturation for a poorly water-soluble model compound in neutral media. Significant formulation development was conducted to identify hydrophilic-enteric combinations which enhanced and stabilized high levels of supersaturation. Finally the last two studies investigate the application of HME to produce solid dispersions containing grades of cyclodextrins. Three poorly water-soluble model drugs were processed at varying parameters by HME to yield amorphous solid dispersions. Analysis of physicochemical interactions revealed cyclodextrins enhance solubility by inclusion and non-inclusion complexation with a drug. Combined, the studies demonstrated the novelty and effectiveness of applying cyclodextrins and thermoplastic polymers in thermal processing to form solid dispersion systems that provide and stabilize enhanced levels of drug supersaturation.