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Application of hot-melt extrusion in the manufacturing of amorphous solid dispersions containing thermally labile drugs
Hot-melt extrusion has gained favor over traditional pharmaceutical formulation techniques in bioavailability/solubility enhancement because it is a solvent-free and continuous operation process that does not require major downstream processing. However, the thermal and mechanical energy applied during the extrusion process can cause chemical degradation of drugs and polymeric carriers In Chapter 1, different methods of preparing amorphous solid dispersions were reviewed. The amorphous solid dispersions generated by different methodologies were compared in terms of physical stability, chemical stability, and the in vivo/in vitro performance. In Chapter 2, the solubility advantage of amorphous solid dispersions was investigated through the heterogeneous phase equilibria analysis. A thermodynamic model for the quantitative assessment of solubility advantage of amorphous solid dispersions was then presented. The thermodynamic model accounted for the chemical potential change as a result of (a) amorphization, (b) ASD formation, and (c) water partition. Experimental solubility advantages of amorphous solid dispersions containing indomethacin was studied by means of intrinsic dissolution measurement. The thermodynamic model allowed predicting the solubility advantage of amorphous solid dispersions. In Chapters 3 and 4, the strategies used in hot-melt extrusion to facilitate manufacture of amorphous solid dispersions containing thermally labile drugs were investigated. Formulation screening based on Flory-Huggins theory, and the utilization of polymer designed for the extrusion process was evaluated in Chapter 3. With the selection of proper formulations, amorphous solid dispersions containing 30% (w/w) carbamazepine were manufactured without any degradation. Improved dissolution properties were also revealed with the final formulations. In Chapter 4, gliclazide was identified as a thermally labile drug with severe degradation by hydrolysis at elevated temperatures, especially when it existed in amorphous or solution form. After optimization of the hot-melt extrusion process, including improved screw design, machine setup, and processing conditions, gliclazide amorphous solid dispersion with ~95% drug recovery was achieved. This study demonstrated the importance of the following factors on drug degradation: (a) changing screw design to facilitate shorter amorphous (melt) residence time, (b) lowering processing temperature to avoid excess thermal exposure, and (c) minimizing processing parameters to reduce unnecessary mechanical energy input.Pharmaceutical Science
Mobilizing Informational Social Capital in Cyber Space: Online Social Network Structural Properties and Knowledge Sharing
Online networks can be construed as social networks in which people engage in interactions, build rela- tionships, share information, and request and extend assistance to each other using electronic communication technologies. Is social capital embedded in online networks? How is such social capital mobilized (i.e., shared)? What structural properties of cyber networks are associated with mobilization of social capital? These questions have drawn the attention of researchers in the areas of social networks, social capital, and online communication. Our research is an initial effort to touch upon these three questions. Whereas most previous research on both conventional and online social networks has favored analysis of either egocentric (i.e., individuals) or bounded (i.e., groups or organizations) networks as the primary unit of analysis, this study investigates online discussion forums that span formal boundaries of organizations, examining their structural properties and patterns of information exchange. We employ a network-based approach to the study of social capital, postulating that mobilization of social capital is contingent on social network properties. Using data from professional online forums devoted to knowledge management, we find that two network properties, core–periphery structure and centralization, are related to the mobilization of informational social capital in online networks. Implications and limitations of this study are discussed and suggestions for future research are provided
Effect of Surfactants on Gas Holdup in Shear-Thinning Fluids
In this study, the gas holdup of bubble swarms in shear-thinning fluids was experimentally studied at superficial gas velocities ranging from 0.001 to 0.02 m·s−1. Carboxylmethyl cellulose (CMC) solutions of 0.2 wt%, 0.6 wt%, and 1.0 wt% with sodium dodecyl sulfate (SDS) as the surfactant were used as the power-law (liquid phase), and nitrogen was used as the gas phase. Effects of SDS concentration, rheological behavior, and physical properties of the liquid phase and superficial gas velocity on gas holdup were investigated. Results indicated that gas holdup increases with increasing superficial gas velocity and decreasing CMC concentration. Moreover, the addition of SDS in CMC solutions increased gas holdup, and the degree increased with the surfactant concentration. An empirical correlation was proposed for evaluating gas holdup as a function of liquid surface tension, density, effective viscosity, rheological property, superficial gas velocity, and geometric characteristics of bubble columns using the experimental data obtained for the different superficial gas velocities and CMC solution concentrations with different surfactant solutions. These proposed correlations reasonably fitted the experimental data obtained for gas holdup in this system
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