Computational fluid dynamics (CFD) studies of a miniaturized dissolution system.

Dissolution testing is an important tool that has applications ranging from fundamental studies of drug-release mechanisms to quality control of the final product. The rate of release of the drug from the delivery system is known to be affected by hydrodynamics. In this study we used computational fluid dynamics to simulate and investigate the hydrodynamics in a novel miniaturized dissolution method for parenteral formulations. The dissolution method is based on a rotating disc system and uses a rotating sample reservoir which is separated from the remaining dissolution medium by a nylon screen. Sample reservoirs of two sizes were investigated (SR6 and SR8) and the hydrodynamic studies were performed at rotation rates of 100, 200 and 400rpm. The overall fluid flow was similar for all investigated cases, with a lateral upward spiraling motion and central downward motion in the form of a vortex to and through the screen. The simulations indicated that the exchange of dissolution medium between the sample reservoir and the remaining release medium was rapid for typical screens, for which almost complete mixing would be expected to occur within less than one minute at 400rpm. The local hydrodynamic conditions in the sample reservoirs depended on their size; SR8 appeared to be relatively more affected than SR6 by the resistance to liquid flow resulting from the screen.

On the role of granule yield strength for the compactibility of granular solids.

The objective of this article was to explore the relationship between mechanical properties of single granules and the evolution in tensile strength and tablet micro-structure. Granules of different expected deformation behavior were used as model materials. It is suggested that the role of plasticity in this context is twofold: firstly, to affect the rate of compactibility and thus the pressure range needed to reach the maximal attained tablet strength and, secondly, to affect the mode of deformation of the granules and thus the maximal attained tablet strength. A decrease in yield pressure of single granules increased the tablet tensile strength at a given compaction pressure. The yield pressure can be controlled by the granule composition and porosity.

Percolative drug diffusion from cylindrical matrix systems with unsealed boundaries.

Release of NaCl in both the axial and radial directions from cylindrical ethyl cellulose tablets were investigated by the alternating ionic current method. The pore structure of the investigated binary mixtures was examined by mercury porosimetry and scanning electron microscopy, and the nm range fractal surface dimension of tablet pore walls was extracted from krypton gas adsorption isotherms. The drug release was shown to consist of two overlapping processes of which the first was ascribed to dissolution of NaCl close to the tablet boundary followed by subsequent diffusion through a thin ethyl cellulose layer and a second from which a porosity percolation threshold of 0.22 could be extracted. As well, a cross-over to effective-medium behaviour at a porosity of approximately 0.44 was observed. The presented findings showed that drug release from matrix tablets with unsealed tablet walls substantially differs from earlier investigated release processes for which the drug has only been allowed to escape through one of the flat tablet surfaces. Thus, the present study brings forward knowledge important for the tailoring of controlled drug delivery vehicles with optimum release patterns.

Drug release modeled by dissolution, diffusion, and immobilization.

This article presents a novel drug release model that combines drug dissolution, diffusion, and immobilization caused by adsorption of the drug to the tablet constituents. Drug dissolution is described by the well-known Noyes-Whitney equation and drug adsorption by a Langmuir-Freundlich adsorption isotherm, and these two processes are included as source and sink terms in the diffusion equation. The model is applicable to tablets that disintegrate into a number of approximately spherical fragments. In order to simplify the analysis it is assumed that liquid absorption, matrix swelling, and tablet disintegration are much faster than drug dissolution and subsequent drug release. The resulting model is shown to yield release characteristics in good agreement with those observed experimentally.