Biomedical subjects

Kees van der Voort Maarschalk

Publications and source records attributed to Kees van der Voort Maarschalk.

5 recordsLinked to original sources

PubMed2006

Granule breakage during drying processes.

The drying of wet granules often involves an unwanted and uncontrolled size reduction. Current FDA PAT guidance stresses importance of process control and understanding. The aim of this study is to determine and understand the breakage phenomena during drying processes in order to control these processes. High shear granulated lactose granules with water as binding liquid were dried during variable periods. Subsequently the (partially) dried granules were exposed to agitation by the impeller and chopper in the granulator. Granule characterization revealed that the change in granule size of (partially) dried granules is dependent on water content and follows a three phase system characterized by a growth, plateau and breakage phase. The derived yield stress of the granules is a function of velocity. From this it is concluded that in the plateau phase above minimum water content, stress behavior of granules can be described with Rumpfs' dynamic granule strength, whereas below minimum water content (breakage phase) granule strength is determined by the solid bridges. The extent and velocity of stress and water content of the granules during the process determine the size reduction phenomena.

Drug Compounding↗

PubMed2006

The determination of relative path length as a measure for tortuosity in compacts using image analysis.

Tortuosity is defined as the ratio of the actual path length from start to goal through the pores to the Euclidean distance (shortest linear distance). However, traditional methods to calculate tortuosity, such as the calculation of tortuosity out of the results from dissolution experiments, do not determine path length directly. In this paper we describe the application of image analysis for direct measurement of path length in order to obtain quantitative information on tortuosity. Several planes in cubic sodium chloride compacts, made by uni-axial compression, were imaged using scanning electron microscopy (SEM). In these images the average path length from top-to-bottom and from left-to-right was calculated, using the gray-weighted distance transform (GDT). As the direct, straight forward path was defined as having a length of unity, the relative path length could be taken as a quantitative measure for the tortuosity. The relative path length through the pores was found to be 1.4-1.6 and the relative path length over the grains was significantly lower (1.0-1.2). In most cases, the relative path length through the pores was significantly higher for the compacts containing small particles than for the compacts made of large particles. The relative path length was also dependent on the direction of the measurement, i.e. in the direction of compression of the compact or perpendicular to it. This indicates anisotropy in structure with the pores preferentially oriented in the direction of compression. It was concluded that this method is a valuable tool for the determination of path length in compacts as a direct measure for tortuosity. It can also be used to evaluate the anisotropy in structure.

Image Processing, Computer-Assisted↗

PubMed2006

The effect of crystal imperfections on particle fracture behaviour.

Micronisation of active pharmaceutical ingredients is a process which is sometimes difficult to control. The main purpose of this study was to assess the effect of the pre-existing flaws in the material to be milled. The rate of breakage of four samples of a model compound (sodium chloride), originating from different sources, was determined in a jet mill. It appeared that each type of sodium chloride has a distinct particle rate of breakage and breakage pattern. The numbers of flaws in the different types of sodium chloride have been determined by immersing the sodium chloride particles in a liquid with the same refractive index. This makes the cracks better visible. Microphotographs were made and flaws were counted manually. The study shows that the flaw density has an impact on the fracture behaviour of particles. The degree of fracture tends to increase with increasing flaw density. The paper shows however that the mechanical properties of the material as well as the starting particle size dominate the significance of the impact of flaws on fracture behaviour.

Crystallization↗

PubMed2005

Location-dependent analysis of porosity and pore direction in tablets.

PURPOSE: Several phenomena in tablets indicate that an inhomogeneous pore distribution is formed during the compaction process. Examples are lamination and the capping of corners. In order to gain an understanding of the relation between structure and compact properties, analyzing the structure in a location dependent manner would be extremely useful. Our aim was to visualize and to quantitatively analyze the pore distribution in compacts. METHODS: This was done by embedding a cubic (sodium chloride) compact with polymer, allowing the compact to be cut without disrupting the structure. By doing so, it was possible to make scanning electron microscopic images from different angles at different locations in the compact. These images were made binary with a two-means cluster algorithm (Isodata) after which the porosity could be calculated. Counting the number of transitions from the pixels in the pores to the pixels in the sodium chloride particles in two perpendicular directions allows us to construct a measure for the anisotropic connectivity of the particles. RESULTS: The results show an increase in porosity toward the bottom of the compact and showed a preferred orientation of the pores in the direction of compression. CONCLUSIONS: The proposed method is suitable for analyzing the pore distribution quantitatively and for evaluating anisotropy.

Anisotropy↗

PubMed2004

Milling of agglomerates in an impact mill.

Milling of agglomerates is one of the common unit operations during preparation of oral dosage forms like capsules and tablets. In literature the breakage of granules is mostly determined after single impact at an ideally formed granule or of single particles. In this paper the breakage behavior of agglomerates after milling with multiple impacts has been studied. It investigates the effects of the formulation and the influences of the mill settings. With respect to the formulation it has been found that both the size of the particles before granulation and the amount of binder used determine the breakage behavior. Both parameters have an influence on the strength of the granule to be milled, where initial particle size has the largest effect. A relation has been found between the strength of granules and the degree of size reduction. Regarding the mill settings, there are no mill parameters which influence the formation of fines independently. Formation of fines is always the result of the total degree of size reduction. It is not possible to achieve a large degree of size reduction without intensive fines formation. The results indicate that it is possible to achieve every desired average particle size. However, when formation of dust has to be reduced, multiple milling steps with separation of in-size particles is necessary.

Administration, Oral↗