Stability Testing of Clinical Samples

The stability program for clinical samples as presented is based on the ICH Tripartite Guideline for Stability Testing of New Drug Substances and Products and the same principles that the program followed throughout the development of a drug product. But the Guideline and the basic principles were adapted to deal with the specific problems encountered with clinical samples. The expiration dates represent minimum shelf lives, storage conditions, and storage periods, and the minimum shelf lives correspond the duration of the clinical trials in phases I to III. Shelf lives are established on the basis of stress and accelerated tests to provide all batches with an open expiration date. They are supported and confirmed by long-term tests conducted under the storage conditions presenting climate zone II, 25°C/60% RH. The self lives determined apply to all the batches of the relevant development stage, although only the batches in the final phase of development originate from a validated manufacturing phase. For different dosages, dosage forms, and packaging materials, the number of batches and analysis is reduced by scientifically based rationalization measures such as bracketing and matrixing. The stability results obtained with clinical samples are a major factor for achieving a comprehensive assessment of the quality of a finished medicinal product. In this way it is possible to establish a link between the quality of clinical batches for phases I-III and the quality of the finished drug product.     

Dissolution Behavior of Griseofulvin Solid Dispersions Using Polyethylene Glycol, Talc, and Their Combination as Dispersion Carriers

Griseofulvin solid dispersions were prepared using polyethylene glycol 6000 (PEG), talc, and their combination as carriers by the solvent method. The dissolution of griseofulvin from these dispersions was studied. It was found that in these carriers the drug dissolution rate was a function of drug loading. The dissolution rate from dispersions prepared using PEG was similar to that from PEG/talc dispersions, especially at a low percentage of drug loading. Dispersions of PEG and PEG/talc provided dissolution rates faster than those from dispersions of talc. The incorporation of talc in PEG yielded dispersions with properties of less tackiness and ease for handling. Dissolution kinetics, based on the Hixson-Crowell equation, was used to determine the characteristics of griseofulvin particles in dispersions. Linear relationships were obtained for PEG and PEG/talc dispersions that indicated the presence of a uniformly sized monoparticulate system, whereas deviation from linearity was observed for talc dispersions. This appeared to be a multiparticulate system in which particles were present as free form and adsorbed form on the surface of talc.     

Unrestricted Hartree-Fock approximation of the extended emery model

We use an unrestricted self-consistent Hartree-Fock approach to calculate the nature of doping states in the three-band Hubbard model. It turns out that for physically relevant parameter values one hole is localized within a small spin-polarized region where five Cu spins are aligned in the same direction. The spin polarization and binding energy between these spinpolaronic states are investigated as a function of different parameters including a Holstein-type electron-phonon coupling on the Cu sites. At higher doping concentration we observe the occurrence of afmon states where the holes are localized in a ring-shaped area. Inside this ring the antiferromagnetic order parameter has inverse sign with respect to the residual antifer-romagnetically ordered plane.     

Analogue micropowered log-domain tone controller for auditoryprostheses

A micropower tone-control circuit comprising two first-order log-domain filters and a subtractor built with MOS transistors in weak inversion is described. The tone-controller is capable of providing bass cut/boost and treble cut operations. This circuit is being used in new designs of a conventional (acoustic) hearing-aid and cochlear implant     

Vibrating cylinder in a cylindrical duct filled with an incompressible fluid of low viscosity

Summary The dynamic interaction of an elastically supported rigid cylinder and a surrounding incompressible fluid in a coaxial cylindrical duct is studied. Attention is focussed on a fluid of low viscosity so that conventional approaches lead to uncertain results. Here a singular perturbation analysis is performed which overcomes the difficulties. As a quantitative result, the complex-valued eigenvalue of the vibrating body in the fluid is computed.     

An image processing IC for backprojection and spatial histogrammingin a pipelined array

The first VLSI digital signal processor that performs both high-precision image backprojection and spatial histogram calculations at raster-scan rates as high as 30 MHz is described. Realized in 1 μm CMOS technology, this 13.3 mm×13.3 mm chip is designed to handle images as large as 1024×1024 12 b pixels. Loadable coefficients and a unified architecture allow this IC to be used with a variety of computed-tomography scanners for image reconstructions, including fan- and parallel-beam reconstruction. This chip also computes the forward Radon transform, which is a spatial histogram, permitting it to be used for iterative reconstruction algorithms. The bit lengths in the fixed-point architecture assure 12 b reconstruction accuracy     

Polymerase chain reaction versus culture for detection of Ureaplasma urealyticum and Mycoplasma hominis in the urogenital tract of adults and the respiratory tract of newborns

The efficiency of the polymerase chain reaction (PCR) was compared with that of culture for detection of Ureaplasma urealyticum and Mycoplasma hominis in 726 clinical specimens comprising 189 gynecological samples, 362 urological samples, and 175 samples from newborn infants. The sensitivity of PCR versus culture was 95% for both organisms, while the sensitivity of culture versus PCR was 91% for Ureaplasma urealyticum and 84% for Mycoplasma hominis. Furthermore, PCR tests were faster than culture tests, allowing the time to diagnosis to be reduced from two to five days to 24 h.     

Reduction of loading effect by tungsten etchback in a magneticallyenhanced reactive ion etcher

The plug loading effect occurring during the etchback of tungsten was investigated in a magnetically enhanced reactive ion etcher using SF ₆/Ar mixtures. It was found that while the plug loading effect is independent of varying SF₆/Ar flow rate ratio and magnetic field intensity, it is reduced under the condition of high selectivity of tungsten relative to TiN which was achieved at high chamber pressure and low RF power. It is proposed that when TiN is used as a glue layer, the W etch rate enhancement in the plug is mainly controlled by a local loading effect. Under the optimized etchback conditions the plug loss was successfully controlled without the tungsten residue left on severe topology     

Growth structure investigation of MgF2 and NdF3 films grown by molecular beam deposition on CaF2(111) substrates

The growth structure of MgF₂ and NdF₃ films grown on polished CaF₂(111) substrates deposited by molecular beam deposition has been investigated using transmission electron microscopy (TEM) of microfractographical and surface replications as well as cross-sectional TEM, atomic force microscopy, packing density, and absorption measurements. It has been shown that by taking advantage of ultrahigh vacuum environments and a special stratification property of MgF₂ and NdF₃ films, the preparation of nanocrystalline films of high packing density and low optical absorption is possible at a substrate temperature of 425 K.     

Broadcast digital subscriber lines

The adoption of asymmetrical digital subscriber lines (ADSL) technology in conjunction with the broadcast digital subscriber lines (BDSL) proposed in this paper could provide a cost effective solution for the introduction of digital video services in the near term. BDSL provides the same digital broadcast video programs to all subscribers through existing twisted pair telephone loops. In this paper, the basics of telephone loop-based digital subscriber lines are first discussed. Then the potential of BDSL is explored in the twisted pair loop plant near end crosstalk (NEXT), far end crosstalk (FEXT), and white noise environment. The capability of BDSL is examined with different serving areas and transmit power levels. The possibility of using orthogonal quadrature amplitude modulation (QAM) to implement a zero guard-band BDSL system is studied. Computer BDSL performance simulations are then presented. The combination of high-bit-rate digital subscriber lines (HDSL), ADSL, and BDSL can provide telephone subscribers many digital broadband services