PubMed HealthSearch

Biomedical subjects

H Leuenberger

Publications and source records attributed to H Leuenberger.

15 recordsLinked to original sources

Formation of a tablet: a site and bond percolation phenomenon.

The concepts of percolation theory are used to elucidate the formation of a tablet by compression of particulate matter. The process of compaction can be considered as a combination of site and bond percolation phenomena. Because of effects of different particle size and shape of the particles in a powder bed and effects of brittle fracture and plastic flow, moisture content of the powder, and finite size of the tablet, no sharp percolation thresholds are expected. Thus, it is interesting to test the validity of the fundamental equation of percolation theory: the power law X = S(p - pc)q, where X is the system property, S is the scaling factor, p is the site occupation or bond formation probability, and q is the critical exponent. This model is, in certain cases, only rigorously valid close to the percolation threshold (range, [+/- 0.1 pc]). Combination of the Heckel equation with an equation derived earlier for the properties (X) of tensile strength (sigma t) and deformation hardness (P) yields a power law with q = 1, S'(sigma t) = sigma tmax/(1 - pc), and S(P) = Pmax/(1 - pc). With respect to the simplifying assumptions made, the power law agrees well with the experimental results obtained. Substantial improvements in the interpretation of the compression-compaction process are possible with these findings, and some interpretations differ from previous ones in earlier publications.

Chemistry, Pharmaceutical

Matrix type controlled release systems: I. Effect of percolation on drug dissolution kinetics.

Matrix type controlled release tablets were prepared by compression of binary mixtures of a soluble brittle model drug (caffeine) and a plastic matrix substance (ethyl cellulose). The drug content of the tablets was varied from 10% to 100% (weight/weight) and the drug dissolution from one flat side of the tablets was studied. By means of percolation theory the release kinetics could be explained over the whole range of drug loadings. For low drug concentrations up to the lower percolation threshold the release was incomplete because most of the drug was encapsulated by the matrix substance. For drug loadings between the lower and the upper percolation threshold the release was matrix-controlled. For high drug loadings a change to zero order dissolution kinetics was observed. Close to the percolation threshold the diffusion coefficient obeys a scaling law, from which a simple equation to estimate the value of the lower percolation threshold was derived and applied to the measured dissolution data. The critical porosity (lower percolation threshold) was found to be 0.35, corresponding to a drug content of about 28% (weight/weight).

Caffeine

Percolation theory and compactibility of binary powder systems.

Defined size fractions of polyethyleneglycol powder (MW = 10,000) were mixed with defined size fractions of alpha-lactose monohydrate in order to study the effect of compaction as a function of the weight ratios of the two excipients. For a precise control of the compression cycle, tablets were compressed on a Universal Testing Machine (Zwick 1478). Tablet tensile strength sigma T was quantified as a function of compressional stress sigma c and relative density rhor r using a two-parameter model with sigma Tmax = maximal tensile strength at zero porosity and gamma = compressibility. The results have been analyzed on the basis of the percolation theory. As soon as the component with the lower mechanical stability is percolating the powder system, tablet hardness is controlled entirely by this component. The percolation threshold is a function of the geometrical arrangement of the particles in the compressed powder system. The expected two percolation thresholds can be distinguished as a function of the composition weight ratios if the particle size distributions of the two components differ enough.

Ascorbic Acid