The Athy—Heckel equation applied to granular agglomerates of basic tricalcium phosphate [3Ca3PO4)2·Ca(OH)2]

It is shown that direct compression grade tricalcium phosphate yields linear Heckel plots only if the particle density used is that obtained by liquid pycnometry or mercury porosimetry. If the true density is used (i.e. that obtained by gas displacement), then linearization is not obtained in a pressure range where bonding evidently occurs. It is shown that the pore volume in the range of diameters from 0.5 to 2 μm decreases as tableting pressure increases, and that bonding is associated with the loss of pores of this size.     

An adaptive non‐conforming finite‐element method for Reissner–Mindlin plates

Adaptive algorithms are important tools for efficient finite‐element mesh design. In this paper, an error controlled adaptive mesh‐refining algorithm is proposed for a non‐conforming low‐order finite‐element method for the Reissner–Mindlin plate model. The algorithm is controlled by a reliable and efficient residual‐based a posteriori error estimate, which is robust with respect to the plate's thickness. Numerical evidence for this and the efficiency of the new algorithm is provided in the sense that non‐optimal convergence rates are optimally improved in our numerical experiments. Copyright © 2003 John Wiley & Sons, Ltd.     

On some interval methods for algebraic,exponential and trigonometric polynomials

New inclusion methods for the simultaneous determination of the zeros of algebraic, exponential and trigonometric polynomials are presented. These methods are realized in real interval arithmetic and do not use any derivatives. Using Weierstrass' correction some modified methods with the increased convergence rate are constructed. Convergence analysis and numerical example are included.     

Linearization of Drug Delivery from Sustained-Release Dosage Forms, Synthetic Gel Systems

A linear, apparent zero-order, in vitro release profile may be approximated from triple-pressed tablets using synthetic gum systems in the first and second press coats. This is coupled with varying concentrations of the actives (Melperone HCl. Diethylpropion HCl, and Dyphylline) in the core and press coats. The approximately linear release function obtained from these tablet systems is in stark contrast to a supposedly prolonged release tablet (comparative formulation) from the literature, which actually releases by the square root of time function characteristic of diffusion control. Addition of a placebo press coat to the outside of the synthetic gum systems simply increases the lag times for release (while the placebo coat is undergoing hydration, etc.). The linearity following the lag is reminiscent of saturation kinetics. Results suggest that the almost linear release profile is a function of the concentration of the various layers (core first and second press coats) coupled with the gelation characteristics of the synthetic gums. This zero order release does not hold for the systems of the comparative formulation taken from the patent literature.     

A priori and a posteriori analysis for a locking-free low order quadrilateral hybrid finite element for Reissner–Mindlin plates

This paper proposes a quadrilateral finite element method of the lowest order for Reissner–Mindlin (R–M) plates on the basis of Hellinger–Reissner variational principle, which includes variables of displacements, shear stresses and bending moments. This method uses continuous piecewise isoparametric bilinear interpolation for the approximation of transverse displacement and rotation. The piecewise-independent shear stress/bending moment approximation is constructed by following a self-equilibrium criterion and a shear-stress-enhanced condition. A priori and reliable a posteriori error estimates are derived and shown to be uniform with respect to the plate thickness t. Numerical experiments confirm the theoretical results.     

Fullerene functionalized polymers

Summary The recent synthesis and macroscopic isolation of C₆₀ (buckminsterfullerene) has stimulated interest in its properties and chemical reactivity. Fullerenes are known to be attacked by nucleophiles and it has been reported that they react with small amines. There is, however, no report on the reaction of fullerenes with polymeric amines. Fullerenes were found to add to amine containing flexible hydrocarbon polymers such as ethylene propylene terpolymer (EPDM-amine) to obtain novel C₆₀ functionalized polymers. These materials are soluble in common solvents. The reaction of the fullerene and polymer was followed by infra-red spectroscopy and viscosity measurements.     

Dynamic flow rates of granular particles

Flow rates (W) of powder and granules are usually measured by letting the particulate solid pass through a stationary orifice. This is not a physical duplication of the event in, for instance, a rotary tablet machine, where the dies move in relation to the powder bed. An apparatus is described by which dynamic flow rates (i.e. flow into a moving orifice) can be measured. These dynamic flow rates (W₂ g/sec) differ from static flow rates. They are subject to the same dependence on particle diameter, d, as static flow rate, i.e.: W₂ ? W_m = ? k(d ? d_m)^s, where “m” refers to maximum and k and s are constants. They also exhibit the same type dependence on orifice opening (P cm) as static flow rates, i.e.W₂ = qPⁿ, where q and n are constants. The values for _n are 3 – 3.25, which is somewhat higher than for static flow where n = 2.3 – 2.6.     

Effect of Drug Solubility in Wet Granulation Fluids on the Dissolution Rates of the Resulting Tablets

One factor in wet granulation processes which affects dissolution rates of the final tablets is shown to be the solubility of the drug substance in the granulating liquid. The relationship is not a direct correlation and a feasible explanation is offered.     

Sensitivity of the Human Eye to Power Frequency Electric Fields

Reports spanning more than a century have shown that tissues associated with the eye are able to respond to local electric fields with impressions of light called electrophosphenes. A finite element analysis of the field distributions in the head near the receptors shows that the 60 Hz threshold for perception of electrophosphenes is approximately 1 V/m. Thus, tissues associated with the eye appear to be among the most sensitive to power frequency electric fields in the human body.     

Aspects of Packaging from NDA <- IND

The strategic decisions regarding package stability in an NDA should be thought out even before the IND stage (hence the inversion of the order of the words NDA and IND in the title). The philosophy of clinical blister packaging is discussed as are the tests necessary to ensure perfection of seal. The principles of molecular and pinhole moisture permeation are discussed. Suggested fractional factorial schemes for package testing are presented