Flow Equations for Free-Flowable Particle Fractions of Sorbitol for Direct Compression: An Exploratory Multiple Regression Analysis of Particle and Orifice Size Influence.

Flowability is among the most important properties of powders, especially when fine particle size fractions need to be processed. In this study, our goal was to find a possibly simple but accurate mathematical model for predicting the mass flow rate for different fractions of the pharmaceutical excipient sorbitol for direct compression. Various regression models derived from the Jones-Pilpel equation for the prediction of the mass flow rate were investigated. Using validation with experimental data for various particle and hopper orifice sizes, we focused on the prediction accuracy of the respective models, i.e., on the relative difference between measured and model-predicted values. Classical indicators of regression quality from statistics were addressed as well, but we consider high prediction accuracy to be particularly important for industrial processing in practice. For individual particle size fractions, the best results (an average prediction accuracy of 3.8%) were obtained using simple regression on orifice size. However, for higher accuracy (3.1%) in a unifying model, valid in the broad particle size range 0.100-0.346 mm, a fully quadratic model, incorporating interaction between particle and orifice size, appears to be most appropriate.

The influence of stevia on the flow, shear and compression behavior of sorbitol, a pharmaceutical excipient for direct compression.

Good flow and compaction properties are necessary for the manipulation of particulate material in the pharmaceutical industry. The influence of the addition of an alternative sweetener, rebaudioside A, in a concentration 0.2% w/w and 0.5% w/w on the flow, shear and compaction properties of sorbitol for direct compaction, Merisorb® 200, was investigated in this work. Rebaudioside A worsened the flow properties of sorbitol: the Hausner ratio, the compressibility index and the mass flow rate through the aperture of a model hopper. Using a Jenike shear cell revealed a significant increase in cohesion leading to the decrease of the flow function; moreover, the addition of rebaudioside A increased the total energy for compression of tablets and plasticity estimated by the force-displacement method. Finally, the tablets showed a higher tensile strength and needed longer time to disintegrate compared to the tablets made of sorbitol itself. In view of the results for the free-flowable excipient, sorbitol, the effects of stevia even for a 0.2% w/w concentration have to be carefully considered, particularly whenever used in pharmaceutical formulations of poor flow properties.

Fractal aspects of the flow and shear behaviour of free-flowable particle size fractions of pharmaceutical directly compressible excipient sorbitol.

Flowability of powder excipients is directly influenced by their size and shape although the granulometric influence of the flow and shear behaviour of particulate matter is not studied frequently. In this work, the influence of particle size on the mass flow rate through the orifice of a conical hopper, and the cohesion and flow function was studied for four free-flowable size fractions of sorbitol for direct compression in the range of 0.080-0.400 mm. The particles were granulometricaly characterized using an optical microscopy; a boundary fractal dimension of 1.066 was estimated for regular sorbitol particles. In the particle size range studied, a non-linear relationship between the mean particle size and the mass flow rate Q10 (g/s) was detected having amaximum at the 0.245mm fraction. The best flow properties of this fraction were verified with aJenike shear tester due to the highest value of flow function and the lowest value of the cohesion. The results of this work show the importance of the right choice of the excipient particle size to achieve the best flow behaviour of particulate material.Key words: flowability size fraction sorbitol for direct compaction Jenike shear tester fractal dimension.

The effect of the size of a conical hopper aperture on the parameters of the flow equation of sorbitol and its size fractions.

Determination of the rate of gravitational flow through a hopper aperture is one of the most widely used methods for the evaluation of flowability properties of pharmaceutical materials. This work studies the influence of the diameter of a conical hopper aperture in the range of 0.6-1.5 cm on the mass flow rate Q (g/s) of the pharmaceutical excipient, sorbitol, for direct compression (Merisorb 200, MS 200) and its size fractions in the range of 0.080-0.400 mm in order to recommend the appropriate aperture size for testing. Non-linear dependence of the flow rate on the aperture diameter is modeled by the Jones-Pilpel power equation. Using the actual parameters of the power equation, the precision of the mass flow rate prediction was the basic criterion in optimization of the orifice diameter. It was detected experimentally that for the evaluation of the flow rate of MS 200 and its size fractions in the range used a 1.0 cm aperture is recommended, which allows the most precise prediction of the flow rate.Key words: particulate material excipient, flow equation conical hopper size fraction.