The Pharmaceutical Use of Captisol®: Some Surprising Observations

The purpose of this paper is to share some recent observations on the pharmaceuticaluses and properties of Captisol^® or SBE_7M--CD in controlled porosity osmotic pump tablets (CP-OPT) and the underlying mechanism/sthat lead to apparent zero-order drug release pattern. It would have been simple toattribute the apparent zero-order release mechanism/s of poorly water-soluble drugsfrom CP-OPTs and pellets utilizing Captisol^®as both a solubilizing andosmotic agent, to purely osmotic and diffusional components. However, the mechanismmay be more related to a counterbalancing of physical properties as the concentration of Captisol^®changes within the matrix. Specifically, the initial concentration of Captisol^®within a core is 0.3–0.4M. When this drops to lower values an osmotic pressure drop occurs across the membrane. Therefore, drug release should not follow apparent zero-order kinetics if all the drug is solubilized. However, as the viscosity within the tablet also drops, the apparent diffusion coefficient of both Captisol^® and drug increases. Therefore, it appears that there is an initial resistance (hydraulic pressure) to fluid flow from the tablet through the rate-limiting microporous membrane. This resistance decreases so that even as osmotic pressure and concentration differences drop with time, counterbalancing faster release occurs. Osmotic driving force appears to be the most important initial driving force but a diffusional component becomes more significant with time.     

Fluorescence-dip infrared spectroscopy and predissociation dynamics of OH A 2Sigma+ (v = 4) radicals

Fluorescence-dip infrared spectroscopy, an UV-IR double-resonance technique, is employed to characterize the line positions, linewidths, and corresponding lifetimes of highly predissociative rovibrational levels of the excited A (2)Sigma(+) electronic state of the OH radical. Various lines of the 4 <--2 overtone transition in the excited A (2)Sigma(+) state are observed, from which the rotational, centrifugal distortion, and spin-rotation constants for the A (2)Sigma(+) (v = 4) state are determined, along with the vibrational frequency for the overtone transition. Homogeneous linewidths of 0.23-0.31 cm(-1) full width at half maximum are extracted from the line profiles, demonstrating that the N = 0 to 7 rotational levels of the OH A (2)Sigma(+) (v = 4) state undergo rapid predissociation with lifetimes of < or =23 ps. The experimental linewidths are in near quantitative agreement with first-principles theoretical predictions.     

NMR studies on dimethyl selenide and dimethyl telluride oriented in the nematic phase of a liquid crystal

¹H NMR spectra of dimethyl selenide with ¹³C and ⁷⁷Se satellites and of dimethyl telluride with ¹³C, ¹²³Te and ¹²⁵Te satellites have been investigated. The structural information has been derived and is found to be in good agreement with microwave results for dimethyl selenide. For dimethyl telluride our results disagree with earlier data obtained by extrapolation from similar molecules.     

Artificial polypeptide scaffold for protein immobilization

An artificial polypeptide scaffold composed of surface anchor and protein capture domains was designed and expressed in vivo. By using a mutant E. coli phenylalanyl-tRNA synthetase, the photoreactive amino acid para-azidophenylalanine was incorporated into the surface anchor domain. Octyltrichlorosilane-treated surfaces were functionalized with this polypeptide by spin coating and photocrosslinking. The resulting protein films were shown to immobilize recombinant proteins through association of coiled coil heterodimer.     

Tritium in Lebensmitteln

To investigate the natural tritium content of foods a combustion apparatus was developed, in which nearly 100 ml of water are obtained in one operation from foods of any composition. To measure the tritium activity of this combustion water in the liquid scintillation spectrometer, the interfering combustion products are removed by distillation. The construction and operation of the combustion apparatus and of the water purification system are described.     

Scalar conservation laws with discontinuous flux function: I. The viscous profile condition

The equation , whereH is Heaviside's step function, appears for example in continuous sedimentation of solid particles in a liquid, in two-phase flow, in traffic-flow analysis and in ion etching. The discontinuity of the flux function atx=0 causes a discontinuity of a solution, which is not uniquely determined by the initial data. The equation can be written as a triangular 2×2 non-strictly hyperbolic system. This augmentation is non-unique and a natural definition is given by means of viscous profiles. By a viscous profile we mean a stationary solution ofu _t +(F ) _x =u _xx , whereF is a smooth approximation of the discontinuous flux, i.e.,H is smoothed. In terms of the 2×2 system, the discontinuity atx=0 is either a regular Lax, an under-or overcompressive, a marginal under- or overcompressive or a degenerate shock wave. In some cases, depending onf andg, there is a unique viscous profile (e.g. undercompressive and regular Lax waves) and in some cases there are infinitely many (e.g. overcompressive waves). The main purpose of the paper is to show the equivalence between a previously introduced uniqueness condition for the discontinuity of the solution atx=0 and the viscous profile condition.     

The coupling of supercritical fluid chromatography and field ionization time-of-flight high-resolution mass spectrometry for rapid and quantitative analysis of petroleum middle distillates

We report the first coupling of supercritical fluid chromatography (SFC) with field ionization time-of-flight high-resolution mass spectrometry (FI-ToF HRMS), in parallel with ultraviolet (UV) detection and flame ionization detection (FID), for rapid and quantitative analysis of petroleum middle distillates. SFC separates petroleum middle distillates into saturates and 1- to 3-ring aromatics. FI generates molecular ions for hydrocarbon species eluted from the SFC. The high resolution and exact mass measurements by ToF mass spectrometry provide elemental compositions of the molecules in the petroleum product. The amounts of saturates and aromatic ring types were quantified using the parallel SFC-FID assisted by SFC-UV. With a proper carbon-number calibration, the detailed composition of the petroleum middle distillate was rapidly determined.     

Removal of graphite by oxidation with perchloric acid plus periodic acid: Inapplicability to the spectrophotometric determination of manganese in steel

An attempt has been made to improve the Willard and Greathouse periodate method for the determination of manganese in high-carbon steel and cast iron by oxidizing the graphite with periodic acid in the presence of perchloric acid and phosphoric acid. Graphite is rapidly oxidized at 150° by this mixture but manganese is lost by volatilization as the heptoxide and decomposition of the latter on hot surfaces to manganese dioxide. No way was found for either the quantitative removal and recovery of manganese by volatilization or for quantitative return to the main solution. The spectrophotometric determination of manganese in the supernatant liquid after allowing graphite to settle yields imprecise but not wholly unacceptable results; for the highest accuracy, graphite should be removed along with silica following dehydration of the latter with perchloric acid.