Development of a Trans-Mucosal Controlled-Release Device for Systemic Delivery of Antianginal Drugs Pharmacokinetics and Pharmacodynamics

Oral mucosa is well-known to be one of the best routes for drug absorption. But very few R & D works have been initiated to investigate the feasibility of using this site to control drug delivery. A transmucosal controlled-release device, which is capable of achieving excellent absorption and controlled release of drugs, has been developed. The device is a tabletshaped mucoadhesive system which is composed of two layers. The upper layer is a fast-release layer and the lower layer is a sustained-release layer, and designed to be applied between buccal and gingival mucosae. Both layers are formulated from synthetic polymers to control the release of drugs.

Isosorbide dinitrate(ISDN), a well-documented antianginal drug, is known to be susceptible to extensive presystemic elimination when taken orally. It was used as the candidate drug and the systemic bioavailability was studied in human and observed to be improved by as much as 5 fold when compared to a marketed oral sustained-release tablet; On the other hand, much smaller amount of metabolites was formed. The plasma profile of ISDN has also been observed to be substantially prolonged (12 hrs as compared to less than 1 hr for sublingual tablet and spray product on the market). These observations have demonstrated that this device is capable of not only bypassing hepatic “first-pass” metabolism but also having a sustainedrelease property of prolonging the release of ISDN.

Clinical studies performed in the anginal patients for up to one year have demonstrated the therapeutic benefits of this device in achieving a substantial reduction in the frequency of anginal attacks.

This type of device was also applied to the systemic delivery of another antianginal drug, Nifedipine, by employing a formulation with longer sustained drug release property. Again, the clinical results demonstrated that a prolonged duration of therapeutic plasma concentration has also been accomplished.     

Change of characteristics of desulfurization and denitrification by combustion flue gas composition and electrode configuration under pulsed corona discharge

Laboratory-scale and parametric experiments of SO₂ and NO_x removal from the simulated combustion gas by pulsed corona discharge have been performed by changing the combustion gas composition and temperature, the electrode configuration of plasma reactor, and the polarity of high-voltage electrode. The following results are obtained: 1) the higher the concentration of H₂O and O₂, the higher the efficiency of desulfurization and denitrification at the same specific input; 2) the pulsed corona discharge with a voltage pulsewidth as short as 200 ns of negative polarity shows the possibility to attain almost 90 percent deSO_x and deNO_x efficiency at the specific discharge input of 20 J/g, which is almost the same as the specific input in the electron-beam process; 3) the deNO_x characteristics show a little temperature dependence in the range of 70 to 130°C, but the deSO_x efficiency increases rapidly in the temperature region below 100°C suggesting the thermochemical dependence of deSO_x reaction; 4) when desulfurization and denitrification proceed, the white dendritic powder deposits on the plasma reactor whose composition is identified to be 49 mol% (NH₄)₂SO₄ and 47 mol% of 2NH₄NO₃ · (NH₄)₂SO₄, and the ratio of SO₂, NO and NH₃ of the deposit is almost equal to that of supplied gas.     

Mechanical stress control in a VLSI-fabrication process: a method for obtaining the relation between stress levels and stress-induced failures

An ideal fabrication process is designed to minimize mechanical stress in semiconductor devices and to improve device reliability. Mechanical stress levels were predicted by in-house simulations supported by a thin-film database. These stress levels were correlated with stress-induced defects by TEM analysis supported by fail bit addressing on matured megabit SRAMs. Amorphous-doped silicon film with various annealing temperatures were used for the gate electrode to change the mechanical stress in devices and to get the direct relationship between predicted stress levels and stress related defects. The authors describe brief guidelines for suppressing dislocations in the small geometry shallow-trench isolation process utilizing this system. Polysilicon thickness in the W-polycide gate electrode is designed to minimize mechanical stress in the gate oxide and to suppress the gate oxide failure in probe and class tests. Moreover, critical stress generates dislocations during post source/drain ion implantation anneal obtained by a ball indentation method. This indicated that lower temperature anneal is effective in suppressing the dislocations. A two-step anneal was introduced to suppress dislocations and to enable higher ion activation.     

Using a GPU to Accelerate Die and Mold Fabrication

The authors present a GPU-based method for generating and verifying cutter paths for numerically controlled milling. A CAM system based on this technology is now employed in production at Mazda Motor Corporation for manufacturing stamping dies. This system can compute cutter paths more than 20 times faster than previous methods     

Stochastic system transformation using generalized orthonormal basis functions with applications to continuous-time system identification

This paper studies the system transformation using generalized orthonormal basis functions that include the Laguerre basis as a special case. The transformation of the deterministic systems is studied in the literature, which is called the Hambo transform. The aim of the paper is to develop a transformation theory for stochastic systems. The paper establishes the equivalence of continuous and transformed-discrete-time stochastic systems in terms of solutions. The method is applied to the continuous-time system identification problem. It is shown that using the transformed signals the PO-MOESP subspace identification algorithm yields consistent estimates for system matrices. An example is included to illustrate the efficacy of the proposed identification method, and to make a comparison with the method using the Laguerre filter.     

Steam absorption process of water/LiBr system inside vertical small bore pipes

In a previous paper, a numerical model for absorption within vertical pipes was proposed and compared with the experiments. Agreements were good for pipes with an OD 28–15 mm but at 10 mm pipe experiments fell below the predicted values. For smaller diameters, the difference between the surface area of the falling liquid film and that of the outer surface of the pipe is not negligible and the thickness of the liquid film is also not negligible. In this paper a new model is formulated in cylindrical coordinates and experiments using pipes with 9.52 mm and 7 mm OD are done. Smooth pipes and two kinds of internally finned pipes, originally developed and used to enhance the heat transfer characteristics of the evaporator and condenser of a refrigerator using HFC as refrigerant, are tested in the experiments. The absorption performance is enhanced by 30% when compared to the smooth pipes, but the difference between the finned pipes is small. © 2004 Wiley Periodicals, Inc. Heat Trans Asian Res, 34(1): 18–28, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/htj.20040     

Observations of high temperature impinging-jet boiling phenomena

A high-speed video camera and microphone were used to capture the flow behavior and boiling sound of a free-surface water jet impinging on a high temperature surface during quench cooling. It was found that depending on the superheat of the surface considerably different flow patterns appeared. For cases where the initial surface temperature was above about 300 °C an almost explosive pattern appeared. This was in contrast to slightly lower temperatures where a liquid sheet flow structure was apparent. The change in phenomena was accompanied by a sudden change in the boiling sound and an increase in the heat transfer rate.     

Development of InxGa1−xAs-based ohmic contacts for p-type GaAs by radio-frequency sputtering

In_xGa_1−xAs-based ohmic contacts which showed excellent contact properties for n-GaAs were demonstrated to be applicable to p-GaAs ohmic contacts. These contacts, prepared by radio-frequency sputtering, provided low contact resistance (0.2 Ω-mm), excellent thermal stability, smooth surface, and good reproducibility. The contact resistances had a weak dependence on the annealing temperatures, which was desirable in a manufacturing view point. This weak temperature dependence was explained to be due to a unique Schottky barrier height at the metal/p-In_xGa_1−xAs interface which does not depend on the In concentration in the In_xGa_1−xAs layer. The present experiment showed the possibility of simultaneous preparation of ohmic contacts for both n and p-GaAs using the same contact materials.     

A small pixel CMD image sensor

A charge modulation device (CMD) imager with pixel dimensions of 7.3 μm(H)×7.6 μm(V) was designed, fabricated, and examined. These pixel dimensions are suitable for an HDTV imager with a 1-in image format. The optical aperture ratio is 34%. The effective number of pixels in the imager is 660 horizontal and 492 vertical. The saturation signal current is 17 μA/pixel at an exposure of 1 lx-s with good linearity of photoconversion characteristics. The peak of its spectral response occurs at a wavelength of 575 nm. The blooming suppression ratio of the CMD was measured to be -122 dB. The sensor produces a high-quality image with no degradation in spatial resolution and no image lag. These features show that the CMD imager is eminently suitable for a further high-resolution imager sensor