Focused beam reflectance method as an innovative (PAT) tool to monitor in-line granulation process in fluidized bed.

Fluidized bed granulation is a commonly used unit operation in the pharmaceutical industry. But still to obtain and control the desired granule size is challenging due to many process variables affecting the final product. Focused beam reflectance measurement (FBRM, Mettler-Toledo, Switzerland) is an increasingly popular particle growth analysis technique. FBRM tool was installed in two different locations inside a fluidized bed granulator (GPCG2, Glatt, Binzen) in order to monitor the granulation growth kinetics. An experimental design was created to study the effect of process variables using FBRM probe and comparing the results with the one's measured by sieve analysis. The probe location is of major importance to get smooth and robust curves. The excess feeding of binder solution might lead to agglomeration and thus to process collapse, however this phenomenon was clearly detected with FBRM method. On the other hand, the process variables at certain levels might affect the FBRM efficiency by blocking the probe window with sticky particles. A good correlation was obtained (R(2) = 0.95) between FBRM and sieve analysis mean particle size. The proposed in-line monitoring tool enables the operator to select appropriate process parameters and control the wet granulation process more efficiently.

Development strategies for herbal products reducing the influence of natural variance in dry mass on tableting properties and tablet characteristics.

One "Quality by Design" approach is the focus on the variability of the properties of the active substance. This is crucially important for active substances that are obtained from natural resources such as herbal plant material and extracts. In this paper, we present various strategies for the development of herbal products especially taking into account the natural batch-to-batch variability (mainly of the dry mass) of tablets that contain a fixed amount of tincture. The following steps in the development have been evaluated for the outcome of the physico-chemical properties of the resulting tablets and intermediates: concentration of the tincture extracted from Echinacea fresh plant, loading of the concentrate onto an inert carrier, the respective wet granulation and drying step, including milling, and the adjuvant excipients for the tablet compression step. The responses that were investigated are the mean particle size of the dried and milled granulates, compaction properties and disintegration time of the tablets. Increased particle size showed a significant increase of the disintegration time and a decrease of the compaction properties. In addition, our results showed that the particle size has a great dependency on the ratio of liquid to carrier during the wet granulation process. Thus, the variability of the respective parameters tested was influenced by the performed strategies, which is how the tincture correlated to its dry mass and the relation of the amount of carrier used. In order to optimize these parameters, a strategy considering the above-mentioned points has to be chosen.

Investigating the effect of particle size and shape on high speed tableting through radial die-wall pressure monitoring.

Investigating particle properties such as shape and size is important in understanding the deformation behavior of powder under compression during tableting. Particle shape and size control the pattern of powder rearrangement and interaction in the die and so the final properties of the compact. The aim of this study was to examine the effect of particle size and shape on compactability. Particle friction and adhesion were investigated through radial die-wall (RDW) pressure monitoring. To fulfill this aim, powders and granules of different sizes and shapes of materials with different compaction behaviors were used. Compaction simulation using the Presster with an instrumented die was applied. Small particle size increased residual die-wall pressure (RDP) and maximum die-wall pressure (MDP) (p<0.05) for plastic and viscoelastic materials, respectively, while big particle size had an opposite effect. No effect was found on brittle material, however big particle size showed higher friction for such materials. Regarding morphology, fibrous elongated particles of microcrystalline cellulose had less friction tendency to the die-wall in comparison to rugged surface mannitol particles. RDW pressure monitoring is a useful tool to understand the compactability of particles in respect to size and shape.