Colonic drug delivery using amylose films: the role of aqueous ethylcellulose dispersions in controlling drug release

Amylose, a plant polysaccharide from starch, can be combined with ethylcellulose to produce a film coating capable of effecting colon specific drug release from a dosage form through bacterial fermentation of the amylose component. Ethylcellulose is present in the system as a structuring agent in the form of the aqueous dispersion Surelease^® grade EA-7100. There are, however, two other grades of Surelease^® (E-7-7050 and E-7-19010), which vary slightly in terms of their composition. The aim of the study was to establish whether these grades differ in their drug release profiles, when used as a film coat, either as one-component coatings, or in combination with amylose. The dissolution profiles of Surelease^® coated pellets were investigated and it was found that there was no difference between the grades when used as coating materials on their own. However, when used in combination with amylose, it was found that grade EA-7100 showed retardation of drug release in simulated upper gastro-intestinal (GI) conditions, whereas grades E-7-7050 and E-7-19010 did not limit the release to the same extent. E-7-19010 showed very poor controlled release properties when combined with amylose. These differences could not be attributed to the minimum film forming temperature (MFT) of the coating formulation, which was found to be independent of the grade of Surelease^®. It was also confirmed that the film coated pellets prepared from amylose and EA-7100 showed good release in human faecal slurry, i.e. simulated colonic conditions. It was concluded that the grades of Surelease^®, when combined with amylose, are not interchangeable.     

The synthesis, characterisation and reactivity of 2-phosphanylethylcyclopentadienyl complexes of cobalt, rhodium and iridium

2-Phosphanylethylcyclopentadienyl lithium compounds, Li[C(5)R'(4)(CH(2))(2)PR(2)] (R = Et, R' = H or Me, R = Ph, R' = Me), have been prepared from the reaction of spirohydrocarbons C(5)R'(4)(C(2)H(4)) with LiPR(2). C(5)Et(4)HSiMe(2)CH(2)PMe(2), was prepared from reaction of Li[C(5)Et(4)] with Me(2)SiCl(2) followed by Me(2)PCH(2)Li. The lithium salts were reacted with [RhCl(CO)(2)](2), [IrCl(CO)(3)] or [Co(2)(CO)(8)] to give [M(C(5)R'(4)(CH(2))(2)PR(2))(CO)] (M = Rh, R = Et, R' = H or Me, R = Ph, R' = Me; M = Ir or Co, R = Et, R' = Me), which have been fully characterised, in many cases crystallographically as monomers with coordination of the phosphorus atom and the cyclopentadienyl ring. The values of nu(CO) for these complexes are usually lower than those for the analogous complexes without the bridge between the cyclopentadienyl ring and the phosphine, the exception being [Rh(Cp'(CH(2))(2)PEt(2))(CO)] (Cp' = C(5)Me(4)), the most electron rich of the complexes. [Rh(C(5)Et(4)SiMe(2)CH(2)PMe(2))(CO)] may be a dimer. [Co(2)(CO)(8)] reacts with C(5)H(5)(CH(2))(2)PEt(2) or C(5)Et(4)HSiMe(2)CH(2)PMe(2) (L) to give binuclear complexes of the form [Co(2)(CO)(6)L(2)] with almost linear PCoCoP skeletons. [Rh(Cp'(CH(2))(2)PEt(2))(CO)] and [Rh(Cp'(CH(2))(2)PPh(2))(CO)] are active for methanol carbonylation at 150 degrees C and 27 bar CO, with the rate using [Rh(Cp'(CH(2))(2)PPh(2))(CO)] (0.81 mol dm(-3) h(-1)) being higher than that for [RhI(2)(CO)(2)](-) (0.64 mol dm(-3) h(-1)). The most electron rich complex, [Rh(Cp'(CH(2))(2)PEt(2))(CO)] (0.38 mol dm(-3) h(-1)) gave a comparable rate to [Cp*Rh(PEt(3))(CO)] (0.30 mol dm(-3) h(-1)), which was unstable towards oxidation of the phosphine. [Rh(Cp'(CH(2))(2)PEt(2))I(2)], which is inactive for methanol carbonylation, was isolated after the methanol carbonylation reaction using [Rh(Cp'(CH(2))(2)PEt(2))(CO)]. Neither of [M(Cp'(CH(2))(2)PEt(2))(CO)] (M = Co or Ir) was active for methanol carbonylation under these conditions, nor under many other conditions investigated, except that [Ir(Cp'(CH(2))(2)PEt(2))(CO)] showed some activity at higher temperature (190 degrees C), probably as a result of degradation to [IrI(2)(CO)(2)](-). [M(Cp'(CH(2))(2)PEt(2))(CO)] react with MeI to give [M(Cp'(CH(2))(2)PEt(2))(C(O)Me)I] (M = Co or Rh) or [Ir(Cp'(CH(2))(2)PEt(2))Me(CO)]I. The rates of oxidative addition of MeI to [Rh(C(5)H(4)(CH(2))(2)PEt(2))(CO)] and [Rh(Cp'(CH(2))(2)PPh(2))(CO)] are 62 and 1770 times faster than to [Cp*Rh(CO)(2)]. Methyl migration is slower, however. High pressure NMR studies show that [Co(Cp'(CH(2))(2)PEt(2))(CO)] and [Cp*Rh(PEt(3))(CO)] are unstable towards phosphine oxidation and/or quaternisation under methanol carbonylation conditions, but that [Rh(Cp'(CH(2))(2)PEt(2))(CO)] does not exhibit phosphine degradation, eventually producing inactive [Rh(Cp'(CH(2))(2)PEt(2))I(2)] at least under conditions of poor gas mixing. The observation of [Rh(Cp'(CH(2))(2)PEt(2))(C(O)Me)I] under methanol carbonylation conditions suggests that the rhodium centre has become so electron rich that reductive elimination of ethanoyl iodide has become rate determining for methanol carbonylation. In addition to the high electron density at rhodium.     

Analysis of a compliantly suspended acoustic velocity sensor

The dynamics of a compliantly suspended acoustic velocity sensor having a spherical geometry are analyzed using theory and experiment. The analysis starts with a review of the motion associated with an unconstrained solid sphere when subjected to an acoustic plane wave in an unbounded inviscid fluid medium. The theory is then modified to account for the inclusion of an inertial sensor and an external suspension system. Accordingly, the open-circuit receiving response of a geophone-based and accelerometer-based device is derived. Density variations associated with the sphere and the surrounding fluid medium are assessed along with the effects fluid viscosity. Wave effects in the sphere and the suspension system are also analyzed.     

Simulated moving columns technique for chiral liquid chromatography

Enantioselectivity of chiral selectors is often relatively low in chiral HPLC. For difficult chiral separations, often only partial resolution is obtained rather quickly by column and mobile phase screening, and, by trial-and-error, additional method optimization is required to achieve complete resolution. This paper describes the development of a novel column-switching technique called "simulated moving columns" (SMC) to quickly achieve complete chiral resolution on columns with limited enantioselectivity. The simulated moving columns (SMC) technique uses two (2) or three (3) short chiral HPLC columns connected in series, and forces the unresolved enantiomers to recycle exclusively through the columns until sufficient resolution is attained. In effect, SMC helps to achieve chiral resolution by virtually multiplying the column length, thus enhancing separation efficiency and resolution, without increasing backpressure. Comparison of the standard non-SMC approach with SMC, and selected applications of chiral separations of pharmaceutical drug molecules are presented. Through measurement and calculation, evaluation of off-column band broadening resulting from a two-column SMC system is provided. The results clearly indicate that SMC eliminates the significant band broadening that is inevitable in the closed-loop recycling techniques currently used in preparative chromatography. Furthermore, SMC is not only useful to enhance resolution for analytical and preparative chiral separation, but also has great potential to enhance recovery and purity for difficult chiral preparative chromatography.     

Debye limit of the stochastic rotation operator

A procedure is proposed for calculating in Debye approximation physical quantities related to steady state random thermal motion. The results are expressed in terms of the stochastic rotation operator. Explicit expressions are derived for this operator and its ensemble average in the case of a rotating molecule which is modelled as a sphere, linear rotator or asymmetric rotator. The relevance of these expressions for certain dielectric and nuclear magnetic relaxation processes is considered.     

Fast wavelength-tunable ultra-violet laser source for confocal Fura-2AM imaging

We report a novel wavelength-flexible laser source for three-dimensional ultra-violet imaging. Based on supercontinuum generation in photonic crystal fiber, the resultant broadband laser source extended from λ = 331 nm into the visible region of the spectrum. Using an electronically-controlled filter wheel and filter set with a response time of approximately 50 ms, rapid wavelength selection was performed. The described scheme is capable of exciting the current range of ultra-violet-excited fluorophores and the simple and rapid wavelength control also provides a new approach for fast ratiometric imaging of Fura-2AM, facilitating an easy method of performing quantitative intracellular calcium concentration measurements.     

Ultra-short pulse compression using photonic crystal fibre

A short section of photonic crystal fibre has been used for ultra-short pulse compression. The unique optical properties of this novel medium in terms of high non-linearity and relatively small group velocity dispersion are shown to provide an ideal platform for the standard fibre pulse compression technique used directly on the nano-Joule output pulses from a commercial laser system. We report an order of magnitude reduction of the pulse width to 25 fs FWHM but predict a substantially improved performance with a dedicated fibre design. Good agreement is obtained with a simple model for the spectral broadening in the fibre. PACS 42.65.Re; 42.70.Qs; 42.81.Cn     

The frequency components of fluid-lift forces acting on a cylinder oscillating in still water

A circular cylinder oscillating with sinusoidal motion in still water is a simple experimental model of circular structural members exposed to continuous wave motion. The measured fluid forces are analyzed using a unique Fourier technique from which fluid-force components can be understood and predicted for structural analysis.