Noisy homoclinic pulse dynamics.

The effect of stochastic perturbations on nearly homoclinic pulse trains is considered for three model systems: a Duffing oscillator, the Lorenz-like Shimizu-Morioka model, and a co-dimension-three normal form. Using the Duffing model as an example, it is demonstrated that the main effect of noise does not originate from the neighbourhood of the fixed point, as is commonly assumed, but due to the perturbation of the trajectory outside that region. Singular perturbation theory is used to quantify this noise effect and is applied to construct maps of pulse spacing for the Shimizu-Morioka and normal form models. The dynamics of these stochastic maps is then explored to examine how noise influences the sequence of bifurcations that take place adjacent to homoclinic connections in Lorenz-like and Shilnikov-type flows.

Liquid ropes: a geometrical model for thin viscous jet instabilities.

Thin, viscous fluid threads falling onto a moving belt behave in a way reminiscent of a sewing machine, generating a rich variety of periodic stitchlike patterns including meanders, W patterns, alternating loops, and translated coiling. These patterns form to accommodate the difference between the belt speed and the terminal velocity at which the falling thread strikes the belt. Using direct numerical simulations, we show that inertia is not required to produce the aforementioned patterns. We introduce a quasistatic geometrical model which captures the patterns, consisting of three coupled ordinary differential equations for the radial deflection, the orientation, and the curvature of the path of the thread's contact point with the belt. The geometrical model reproduces well the observed patterns and the order in which they appear as a function of the belt speed.

Comparison of polyethylene glycol and polyoxyethylene stearate as excipients for solid dispersion systems of griseofulvin and tolbutamide I: phase equilibria.

Phase equilibrium diagrams were constructed based on hot-stage microscopy and differential scanning calorimetry of solid dispersions of griseofulvin or tolbutamide in polyethylene glycol 2000 or polyoxyethylene 40 stearate. The solid dispersions were prepared by physical mixing, fusion, and coprecipitation from ethanol. The phase diagrams were largely independent of the method of preparation of the dispersion systems. The diagrams were of the monotectic type for polyethylene glycol 2000 with each drug and for griseofulvin with each excipient, with the monotectic species being the pure drug. Polyoxyethylene 40 stearate with tolbutamide gave eutectic systems in which liquid polyoxyethylene 40 stearate dissolved up to 20% of the tolbutamide. The phase diagrams showed greater solubility of tolbutamide in liquid polyoxyethylene 40 stearate than in polyethylene glycol 2000 but showed a similar solubility of griseofulvin in each experiment. Solid solution formation was not detected.

Comparison of polyethylene glycol and polyoxyethylene stearate as excipients for solid dispersion systems of griseofulvin and tolbutamide II: dissolution and solubility studies.

The effects of joining a long-chain ester group with the polyethylene glycol molecule were studied in solid dispersion systems by comparing the dissolution and solution properties of such systems prepared from polyethylene glycol 2000 with those prepared from the nontoxic, water-soluble, solid excipient polyoxyethylene 40 stearate. Solid dispersion systems of griseofulvin and tolbutamide were prepared by physical mixing, fusion, or coprecipitation from ethanol. The compacted dispersion systems dissolved by progressive erosion, releasing floccules of microcrystals. The released microcrystals of tolbutamide (3--10 micrometer) were smaller than the original drug particles (approximately 20 micrometer), but those of griseofulvin were of similar size to the original particles. In general, the rate of and extent of release of each drug were greater from polyoxyethylene 40 stearate than from polyethylene glycol 2000 dispersions. The aqueous solubility and dissolution rate of nondisintegrating disks of each pure drug increased only slightly in the presence of polyethylene glycol 2000 but increased considerably with increasing concentration of polyoxyethylene 40 stearate due to micellar solubilization. Thus, polyoxyethylene 40 stearate generally is superior to polyethylene glycol 2000 in promoting the dispersion of the drugs in solids, disintegration of the compacted solids, and solubilization of the drug during dissolution.

The filling of molten and thixotropic formulations into hard gelatin capsules.

Problems in the formulation and manufacture of conventional solid dose form products include the variation of fill weight and drug content, dissolution control of poorly water soluble drugs and dust generated during manufacture giving rise to cross contamination. We have examined the application of a liquid filling technique for the manufacture of hard gelatin capsules as a means of overcoming some of these. Filling materials are based on water-soluble hot melt polymers such as polyethylene glycol or water-dispersible thixotropic systems of pharmaceutical oils with thixotropic additives. A Zanasi LZ64 capsule filling machine was adapted to fill liquids using filling pump. No dust is generated during filling and 20 microgram doses of drug can be accurately filled without extensive processing. The formulations are simple and do not require specialist ingredients such as lubricants, binders, disintegrants and flow aids. The method of manufacture is reduced to a simple mixing and direct filling operation. The system may be applied to promote the dissolution of poorly water soluble drugs using solid solutions or solid dispersions. Slow release formulations are also available using suitable retard excipients.