A new method to predict flowability using a microscale fluid bed |
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Authors: | Eetu R?s?nen Osmo Antikainen Jouko Yliruusi |
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Institution: | (1) Pharmaceutical Technology Division, Department of Pharmacy, FIN-00014 University of Helsinki, PO Box 56, Finland |
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Abstract: | 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 (u
mf) 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 experimentalu
mf increased and the fluidization behavior grew worse (Video 2). Principal component analysis (PCA) established that the pressure
difference over the bed as a function of fluidization velocity could be used to characterize the behavior of powders. The
increase in poor fluidization behavior of the powders was in accordance with the increasing amount of paracetamol and with
the increasing weight variation of the tablets. Furthermore, the angle of repose and the flow rate of silicified microcrystalline
cellulose powders were predicted using a partial least squares (PLS) model. The developed method to predict flowability is
a promising approach for use in the preformulation and formulation stages of new drug candidates, for example. |
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Keywords: | fluid bed flowability formulation preformulation |
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