Fluid Bed Granulation Articles

The movement of particles in fluidization processes in a model test reactor has been studied using an imaging technique from medical healthcare: Positron Emission Tomography (PET). With this noninvasive technique, tracer particles were followed o­n their way through the fluidized bed. Experiments were performed with pulses of tracer particles in different alignments. The results give a good impression of both axial and radial distribution of particles in fluidized bed. In this paper, the experimental results confirm the basic assumptions of the model. Our stochastic model captures the dynamic movement of particles qualitatively, but indications are that the system exhibits ‘gulfstreaming’, a feature which is not accounted for in the model, but is common in fluidized beds in practice.




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This paper describes a series of experiments tracing a single radioactive particle in a fluidized bed in an ECAT EXACT HR+ PET camera in order to obtain 3-D paths for an actual bed particle – i.e. a particle typical for the bed material – with a high spatial and temporal resolution. The paper describes how "lines of response" (LORs) were calculated from the binary list-mode files from the camera, and how particle positions (1 per ms) were computed from the LORs. It also gives a condensed account of how the data were analyzed further. The particle movement in the bed is shown graphically, and the findings interpreted in light of the theories o­n mechanisms behind particle movement in fluidized beds. Among other things the issue of fast, short-range movement of particles in fluidized beds is discussed. The findings are consistent with the notion of upward particle motion in the wakes of fluidization bubbles, and downward motion in the bulk.

This study assesses the fluidized bed granulation process for the optimization of a model formulation using in-line near-infrared (NIR) spectroscopy for moisture determination. The granulation process was analyzed using an automated granulator and optimization of the verapamil hydrochloride formulation was performed using a mixture design. The NIR setup with a fixed wavelength detector was applied for moisture measurement. Information from other process measurements, temperature difference between process inlet air and granules (Tdiff), and water content of process air (AH), was also analyzed. The application of in-line NIR provided information related to the amount of water throughout the whole granulation process. This information combined with trend charts of Tdiff and AH enabled the analysis of the different process phases. By this means, we can obtain in-line documentation from all the steps of the processing.

Dilip M. Parikh,

Spray-drying is known to produce predominantly amorphous material because of rapid solidification.1 The detection and control of the amorphous portion of powdered material is of utmost importance, as different physical forms of materials have different physicochemical properties that give rise to significant differences in functionality when used in dosage forms. The influence of spray-drier feed concentration o­n the degree of crystallinity and the crystal form of lactose (β-lactose, anhydrous α-lactose, α-lactose monohydrate) has been described previously.2It is known2 that the spray-drying process can be made to produce completely amorphous lactose particles. Furthermore, it is clear that the amorphous form is unstable and that it will revert to the crystalline form.

HERCULES : Pharmaceutical Technology Report

Eetu Räsänen, Osmo Antikainen, Jouko Yliruusi
AAPS PharmSciTech. 2003; 4(4): article 53. The purpose of this research was to develop a new method to predict the flow behavior of pharmaceutical powders using a multichamber microscale fluid bed. Different amounts of poorly flowing paracetamol were added to various grades of microcrystalline celluloses and silicified microcrystalline cellulose powders. Magnesium stearate was used as a lubricant. Experimental minimum fluidization velocities (umf) were defined using 2 to 4 g (equal to 10 mL) of material (Video 1). The reference flowability of the powders was determined using a specific flow meter. Also, the weight variation of the compressed powders, using a single-punch press, was measured. When the amount of paracetamol in the excipients was increased, the experimental umf increased and the fluidization behavior grew worse (Video 2).

The pharmaceutical industry faces new challenges associated with increased market globalization, demands for cleaner environments, higher customer expectations, the push for increased profitability, tighter FDA regulations, and the ever-increasing demand to reduce time to market. The industry is under pressure to reduce waste and improve process efficiency. The traditional approach of taking a product from laboratory scale to pilot plants and then to production is no longer attractive. Process and product development often are initiated simultaneously, and as a result, rapid prototyping and analysis are required. To meet these challenges, the industry must implement innovation at all phases of product development.

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The authors describe the in-line moisture measurement of a pharmaceutical granulation of lactose, microcrystalline cellulose and crospovidone in a fluid bed granulator–dryer using top sprayed granulating liquid. A near-infrared (NIR) prediction model was developed for moisture on spectra collected during a calibration run. Subsequent granulations were analyzed for moisture content real-time throughout the granulation and drying process using the NIR process instrument.

Granulation is an important step in pharmaceutical solid dosage form processing. The flow and compression characteristics of a formulation are improved through granulation. Also, the content uniformity of the formulation is maintained after blending by the agglomeration of smaller particles to form larger particles through granulation (1).