Ingfried Zimmermann

Measurement of interaction forces between individual powder particles using an atomic force microscope

The atomic force microscope (AFM) was used to investigate the interaction forces between individual particles qualitatively as well as quantitatively. Lactose as a typical excipient for solid drugs was chosen as model substance. The interaction forces were determined between a single particle of crystalline lactose and a tablet of lactose. Their surface topography was characterized by AFM and scanning electron microscopy (SEM) in order to allow a quantitative assessment of the surface roughness and its influence on the measured forces. To analyze the representative surface segments, the minimum and maximum surface roughness of the lactose tablet is determined in dependence of the segment size. The contact area between the tablet and the particle of lactose was quantified by the tip estimation of Villarrubia. Interparticle forces were measured with force volume scans. They allow the determination of the three-dimensional surface structure and, simultaneously, a defined number of force curves in regular distances is taken.

A new approach for the measurement of the tensile strength of powders

A new method and equipment for the determination of the vertical tensile strength of bulk solids is described. It allows for the direct determination of the tensile strength of compacted as well as of almost noncompacted powders. For the experiments lactose and corn starch were used as model substances. The cohesion of a powder determined by means of the Jenike shear cell and the tensile strength measured using the new tensile strength tester (TST) were compared. The influence of the powder porosity on the tensile strength and cohesion, respectively was also investigated. As expected the tensile strengths determined by means of the TST are lower than the cohesions obtained from shear cell measurements. However, the ratio of the cohesions of lactose and corn starch determined by using the shear cell is the same as that calculated from results obtained by means of the TST. The results obtained from the Jenike shear cell are much more sensitive to the sample porosity than those from the TST. This observation can be explained by the different measuring principles. In contrast to the TST, the Jenike shear cell method requires that the powders have to be consolidated to a certain state. The new equipment however allows for the determination of the vertical tensile strengths of noncompacted powders.

Preparation and characterization of shellac-coated anthocyanin pectin beads as dietary colonic delivery system†

SCOPE Anthocyanins are connected with various biological activities. A promising way to enhance the availability of anthocyanins for in situ effects in the lower intestine is colon-specific delivery. METHODS AND RESULTS Shellac and shellac/hydroxypropyl methylcellulose (HPMC) coated anthocyanin amidated pectin beads as dietary colonic delivery systems were successfully prepared by ionotropic gelation and fluid bed Wurster coating with aqueous shellac solution. Release characteristics, studied in vitro and ex vivo using simulated gastric fluid (SGF), ileostomy fluid and colostomy fluid (CF) revealed a retardation of anthocyanins during simulated passage of stomach and ileum as well as the desired release of pigments in the colon. Coating level was identified as an important parameter. By addition of 5 or 15% of the water-soluble polysaccharide HPMC to the shellac film, resistance in SGF was increased due to the plasticizer properties of the polymer. Incorporation of 15% HPMC (w/w based on shellac) into the shellac film additionally led to increased anthocyanin diffusivity and complete release as well as degradation of the formulation in CF. CONCLUSION In the used in vitro and ex vivo model system mimicking the human intestinal transit, the potential of shellac and shellac/HPMC coated anthocyanin amidated pectin beads as dietary colon targeting systems was demonstrated.

Precipitated silica as flow regulator

Flow regulators are added to solid pharmaceutical formulations to improve the flow properties of the powder mixtures. The primary particles of the flow regulators exist in the form of huge agglomerates which are broken down into smaller aggregates during the blending process. These smaller aggregates adsorb at the surface of the solids grains and thus diminish attractive Van-der-Waals-forces by increasing the roughness of the hosts surface. In most cases amorphous silica is used as flow additive but material properties like particle size or bond strength influence the desagglomeration tendency of the agglomerates and thus the flow regulating potency of each silica. For some silica types we will show that the differences in their flow regulating potency are due to the rate and extent by which they are able to cover the surface of the host particles. Binary powder mixtures consisting of a pharmaceutical excipient and an added flow regulator were blended in a Turbula mixer for a defined period of time. As pharmaceutical excipient corn starch was used. The flow regulators were represented by a selection of amorphous silicon dioxide types like a commercial fumed silica and various types of SIPERNAT precipitated silica provided by Evonik-Degussa GmbH, Hanau, Germany. Flowability parameters of the mixtures were characterized by means of a tensile strength tester. The reduction of tensile strength with the blending time can be correlated with an increase in fragmentation of the flow regulator.